SEC61A1 p.Val8=
c.24C>T · VCV4964020
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000509%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.042 | GERP -5.2, phastCons 0.7 |
| Overall | ||
| CADD | 12.27 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,179,784 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,613,700 alleles · very rare
exomes 6/1,461,340 · genomes 0/152,360 · joint denominator
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
- SEC61A1
- Protein
- p.Val8=
- Coding
- c.24C>T
- MANE Select
- NM_013336
- Type
- single nucleotide variant
- Location
- chr3:128052851 (GRCh38)
- Gene constraint
- LOEUF 0.404 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.19 · 16 PDB
- Residue 8
- an α-helix
Similar variants
- SEC61A1 p.Val8Ile Uncertain significance ★ ⚠ same residue
- SEC61A1 p.Leu89Phe Likely pathogenic ★★ same type
- SEC61A1 p.Ile100Thr Uncertain significance ★★ ⚠ same type
- SEC61A1 p.Ile161Thr Uncertain significance ★★ same type
- SEC61A1 p.Val192Ile Uncertain significance ★★ ⚠ same type
- SEC61A1 c.1168-4G>A Benign/Likely benign ★★ same type
- SEC61A1 c.220+128A>G Benign ★★ same type
- SEC61A1 c.220+129A>C 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/sec61a1-p-val8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown