ERGIC3 p.Ala269=
c.807G>A · VCV3846008
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.095 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.86 | GERP 0.12, phastCons 0.98 |
| Overall | ||
| CADD | 13.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/59,990 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00136%
22/1,614,014 alleles · very rare
exomes 19/1,461,868 · genomes 3/152,146 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 14,997 |
| Finnishnot grpmax-eligible | 0.00312% | 32,013 |
| South Asian | 0.0022% | 45,546 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00134% | 74,906 |
| European (non-Finnish) | 0.00102% | 98,336 |
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
- ERGIC3
- Protein
- p.Ala269=
- Coding
- c.807G>A
- MANE Select
- NM_015966
- Type
- single nucleotide variant
- Location
- chr20:35556122 (GRCh38)
- Gene constraint
- LOEUF 0.781 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.05
Similar variants
- ERGIC3 c.718-4A>G Benign ★★ same type
- ERGIC3 p.Leu295= Benign ★★ same type
- ERGIC3 c.686-664G>A Uncertain significance ★ same type
- ERGIC3 c.717+1G>A Uncertain significance ★ same type
- ERGIC3 p.Arg121Gln Uncertain significance ★ ⚠ same type
- ERGIC3 p.Arg163Gln Uncertain significance ★ ⚠ same type
- ERGIC3 p.Arg163Trp Uncertain significance ★ ⚠ same type
- ERGIC3 p.Arg167Cys Uncertain significance ★ ⚠ 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/ergic3-p-ala269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown