SEC31A p.Pro958=
c.2874A>G · rs771768482 · VCV2654847
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0923%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.075 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.55 | GERP -0.43, phastCons 0.017 |
| Overall | ||
| CADD | 7.403 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0923%
South Asian · 84/91,040 alleles
Filtering AF
0.0763%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0705%
Overall
0.0113%
183/1,613,364 alleles · ultra-rare
exomes 173/1,461,266 · genomes 10/152,098 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0923% | 1,084 |
| Middle Eastern | 0.0822% | 1,216 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,204 |
| Admixed American | 0.00834% | 11,992 |
| European (non-Finnish) | 0.00653% | 15,320 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SEC31A
- Protein
- p.Pro958=
- Coding
- c.2874A>G
- MANE Select
- NM_001077207
- dbSNP
- rs771768482
- Type
- single nucleotide variant
- Location
- chr4:82842234 (GRCh38)
- Gene constraint
- LOEUF 0.542 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 68.95 · 2 PDB
- Residue 958
- the 'interaction with pdcd6' region; the 'disordered' region
Similar variants
- SEC31A p.Arg486His Uncertain significance ★★ same type
- SEC31A p.Asp84Gly Uncertain significance ★★ ⚠ same type
- SEC31A p.Cys458Trp Uncertain significance ★★ ⚠ same type
- SEC31A p.Pro945Ser Uncertain significance ★★ ⚠ same type
- SEC31A c.1045-26G>T Benign ★★ same type
- SEC31A c.2154+36G>C Benign ★★ same type
- SEC31A c.2154+8C>T Likely benign ★★ same type
- SEC31A c.2503-29C>A Benign ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/sec31a-p-pro958 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown