# NM_014844.5(TECPR2):c.242_243del (p.Val81fs)

https://sugi.bio/variant/tecpr2-p-val81fs

## Summary

**TECPR2 p.Val81fs (c.242_243del)** is classified **Pathogenic** in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-01-22). No gnomAD frequency available for this variant.

**At a glance:** Pathogenic · review: Single submitter · rsID rs886043167 · 1 submitter · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the TECPR2 gene that is reported as disease-causing, but on limited review, 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 | [TECPR2](https://sugi.bio/atlas/gene/TECPR2/) |
| Protein change (HGVS p.) | p.Val81fs |
| Coding change (HGVS c.) | c.242_243del |
| MANE Select transcript | [NM_014844](https://www.ncbi.nlm.nih.gov/nuccore/NM_014844) |
| dbSNP | [rs886043167](https://www.ncbi.nlm.nih.gov/snp/rs886043167/) |
| Variant type | Microsatellite |
| Location | chr14:102407358-102407359 (GRCh38) |
| ClinVar | [VCV285656](https://www.ncbi.nlm.nih.gov/clinvar/variation/285656/) |

**All HGVS expressions:** `NC_000014.8:g.102873695TG[1]`, `NC_000014.9:g.102407358TG[1]`, `NG_042851.1:g.49447TG[1]`, `NM_001172631.3:c.242_243del`, `NM_014844.5:c.242_243del`

## 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 5.814, GERP 1.93, phastCons 1 — highly conserved position (PP3-type support)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.607, pLI 2.1398e-07. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in exon 3 of 20**, so the transcript is predicted to undergo NMD.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no microsatellite 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.*

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

**TECPR2** population constraint: LOEUF 0.607, pLI 2.1398e-07, missense-Z 2.3384; ClinGen dosage — haploinsufficiency gene assoc. with recessive phenotype, triplosensitivity 0/3. *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 68.27, 38% of residues very-high.

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2016-01-22.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Eurofins Ntd Llc (ga) | Pathogenic | criteria provided, single submitter | clinical testing | 2016-01-22 |

**Reported phenotype names (ClinVar):** not provided, RECLASSIFIED - ADRA2C POLYMORPHISM, RECLASSIFIED - ADRB1 POLYMORPHISM, none provided.

## Similar variants {#similar}

Related TECPR2 variant pages (same residue, condition, or type): [TECPR2 p.Val81=](/variant/tecpr2-p-val81), [TECPR2 p.Glu12fs](/variant/tecpr2-p-glu12fs), [TECPR2 p.Leu225_Cys226insTer](/variant/tecpr2-p-leu225-cys226inster), [TECPR2 p.Thr649fs](/variant/tecpr2-p-thr649fs), [TECPR2 p.Lys471del](/variant/tecpr2-p-lys471del), [TECPR2 c.2578+10CCCGCTCCCTGCT[3]](/variant/tecpr2-c-2578-plus-10cccgctccctgct-3), [TECPR2 c.2578+30_2578+42del](/variant/tecpr2-c-2578-plus-30-2578-plus-42del), [TECPR2 p.Lys471dup](/variant/tecpr2-p-lys471dup).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); 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 2026-10-14); 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 285656). 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.*