# NM_000587.4(C7):c.317del (p.Asp106fs)

https://sugi.bio/variant/c7-p-asp106fs

## Summary

**C7 p.Asp106fs (c.317del)** is classified **Pathogenic** in C7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-11-14). No gnomAD frequency available for this variant; Associated with complement component 7 deficiency.

**At a glance:** Pathogenic · review: No assertion criteria · rsID rs1579848888 · 1 submitter · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the C7 gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to complement component 7 deficiency.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0018290/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [C7](https://sugi.bio/atlas/gene/C7/) |
| Protein change (HGVS p.) | p.Asp106fs |
| Coding change (HGVS c.) | c.317del |
| MANE Select transcript | [NM_001565](https://www.ncbi.nlm.nih.gov/nuccore/NM_001565) (variant reported on NM_000587) |
| dbSNP | [rs1579848888](https://www.ncbi.nlm.nih.gov/snp/rs1579848888/) |
| Variant type | Deletion |
| Location | chr5:40936374-40936374 (GRCh38) |
| ClinVar | [VCV635448](https://www.ncbi.nlm.nih.gov/clinvar/variation/635448/) |

**All HGVS expressions:** `LRG_30:g.31878del`, `LRG_30t1:c.317del`, `NC_000005.10:g.40936374del`, `NC_000005.9:g.40936476del`, `NG_011692.1:g.31878del`, `NM_000587.4:c.317del`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 11.761, GERP 2.29, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. For a truncating variant the loss-of-function impact is position-dependent — C-terminal / last-exon truncations may escape nonsense-mediated decay. *Descriptive; not an applied PVS1 code.*
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 89.67, 71% of residues very-high.

**6 experimental structure(s)** (PDB): [1LV9](https://www.rcsb.org/structure/1LV9), [1O7Y](https://www.rcsb.org/structure/1O7Y), [1O7Z](https://www.rcsb.org/structure/1O7Z), [1O80](https://www.rcsb.org/structure/1O80), [8K2X](https://www.rcsb.org/structure/8K2X), [9P0L](https://www.rcsb.org/structure/9P0L).

## What this gene does {#gene-function}

*Describes the biological roles of C7 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** C7's established molecular role includes chemokine activity.


### Pathways affected {#pathways}

C7 participates in **3 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Chemokine receptors bind chemokines](https://reactome.org/content/detail/R-HSA-380108) | curated |
| [G alpha (i) signalling events](https://reactome.org/content/detail/R-HSA-418594) | curated |
| [Interleukin-10 signaling](https://reactome.org/content/detail/R-HSA-6783783) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** chemokine activity, heparin binding, chemoattractant activity, CXCR3 chemokine receptor binding.

**Biological process:** chemotaxis, G protein-coupled receptor signaling pathway, adenylate cyclase-activating G protein-coupled receptor signaling pathway, T cell chemotaxis, regulation of T cell chemotaxis, negative regulation of angiogenesis.

## Clinical significance {#significance}

**Pathogenic** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2018-11-14.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare | Pathogenic | no assertion criteria provided | clinical testing | 2018-11-14 |

## Associated conditions {#conditions}

[complement component 7 deficiency](https://sugi.bio/atlas/disease/complement-component-7-deficiency/).

**Reported phenotype names (ClinVar):** Complement component 7 deficiency, C7 DEFICIENCY.

## Similar variants {#similar}

Related C7 variant pages (same residue, condition, or type): [C7 c.2350+1del](/variant/c7-c-2350-plus-1del), [C7 p.Asn136fs](/variant/c7-p-asn136fs), [C7 p.Ser212fs](/variant/c7-p-ser212fs), [C7 p.Lys438fs](/variant/c7-p-lys438fs), [C7 c.281-1G>T](/variant/c7-c-281-minus-1g-t), [C7 c.63-1G>A](/variant/c7-c-63-minus-1g-a), [C7 p.Gly379Arg](/variant/c7-p-gly379arg), [C7 p.His643fs](/variant/c7-p-his643fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 635448). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*