SEC61A1 p.Pro22=
c.66A>C · VCV4775933
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00836%, amr)
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 -2.6 | GERP -5.2 |
| Overall | ||
| CADD | 5.468 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00836%
Admixed American · 5/59,822 alleles
Filtering AF
0.00324%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00031%
5/1,613,096 alleles · very rare
exomes 4/1,460,862 · genomes 1/152,234 · 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.Pro22=
- Coding
- c.66A>C
- MANE Select
- NM_013336
- Type
- single nucleotide variant
- Location
- chr3:128052893 (GRCh38)
- Gene constraint
- LOEUF 0.404 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.19 · 16 PDB
- Residue 22
- an α-helix
Similar variants
- 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
- SEC61A1 c.221-53C>T 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-pro22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown