# NM_152515.5(CKAP2L):c.1839T>C (p.Ser613=)

https://sugi.bio/variant/ckap2l-p-ser613

## Summary

**CKAP2L p.Ser613= (c.1839T>C)** is classified **Likely benign** in CKAP2L (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). Ultra-rare (popmax 0.0187%, afr).

**At a glance:** Likely benign · review: Single submitter · rsID rs766132076 · 1 submitter · ultra-rare (popmax 0.0187%, afr)

## For patients & families {#patients}

This is a change in the CKAP2L gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*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.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CKAP2L](https://sugi.bio/atlas/gene/CKAP2L/) |
| Protein change (HGVS p.) | p.Ser613= |
| Coding change (HGVS c.) | c.1839T>C |
| MANE Select transcript | [NM_152515](https://www.ncbi.nlm.nih.gov/nuccore/NM_152515) |
| dbSNP | [rs766132076](https://www.ncbi.nlm.nih.gov/snp/rs766132076/) |
| Variant type | single nucleotide variant |
| Location | chr2:112740991-112740991 (GRCh38) |
| ClinVar | [VCV2651285](https://www.ncbi.nlm.nih.gov/clinvar/variation/2651285/) |

**All HGVS expressions:** `NC_000002.11:g.113498568A>G`, `NC_000002.12:g.112740991A>G`, `NG_041820.1:g.28687T>C`, `NM_001304361.2:c.1344T>C`, `NM_001350494.2:c.1249-1421A>G`, `NM_152515.5:c.1839T>C`, `NR_130712.2:n.1092T>C`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **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 and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **acceptor loss** (Δ 0.22) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP -0.206, GERP -4.1 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 1.821**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI deltas (raw): acceptor loss **0.22**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.00**. Largest is acceptor loss, 5 bp away.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.00**.
  Masked SpliceAI — what Ensembl VEP and the Broad lookup serve by default — is below the reporting threshold here, so those tools show **no splice signal** for this allele. Masking zeroes a loss scored against a position that is not an annotated splice site, and a gain that merely strengthens an existing one, so the raw score above is describing a cryptic site rather than the site the variant sits on. *No ACMG code is assigned either way.*
- Population frequency (gnomAD v4.1): grpmax **0.0187%** (afr) · FAF95 0.0112% · FAF99 0.00905% · 14/74,890 in the highest group · 25/1,610,774 alleles overall — ultra-rare (popmax 0.0187%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 0.0187% | 5,349 |
| Middle Eastern | 0.0165% | 6,072 |
| Admixed American | 0.00834% | 11,993 |
| Remaining individuals (not grpmax-eligible) | 0.00641% | 15,591 |
| European (non-Finnish) | 8.49e-05% | 1,177,368 |

*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.*

## Gene constraint & dosage {#gene-context}

**CKAP2L** population constraint: LOEUF 0.72, pLI 0.00013949, missense-Z -0.018164. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 54.68, 8% of residues very-high.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-05-01.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2023-05-01 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related CKAP2L variant pages (same residue, condition, or type): [CKAP2L p.Arg206Gly](/variant/ckap2l-p-arg206gly), [CKAP2L p.Arg284Trp](/variant/ckap2l-p-arg284trp), [CKAP2L p.Arg347Lys](/variant/ckap2l-p-arg347lys), [CKAP2L p.Arg688Gln](/variant/ckap2l-p-arg688gln), [CKAP2L p.Cys725Ser](/variant/ckap2l-p-cys725ser), [CKAP2L p.Gln428Arg](/variant/ckap2l-p-gln428arg), [CKAP2L p.Glu462Val](/variant/ckap2l-p-glu462val), [CKAP2L p.Ile283Leu](/variant/ckap2l-p-ile283leu).

### 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 2651285). 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.*