EYS p.Ala2276=
c.6828C>T · rs373606872 · VCV991103
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.156%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.019 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.15 | GERP -0.38 |
| Overall | ||
| CADD | 1.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.156%
African / African-American · 114/72,894 alleles
Filtering AF
0.133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.124%
Overall
0.00777%
120/1,544,884 alleles · rare
exomes 52/1,392,730 · genomes 68/152,154 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.156% | 639 |
| Admixed American | 0.00785% | 12,744 |
| European (non-Finnish) | 0.000175% | 570,278 |
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
- EYS
- Protein
- p.Ala2276=
- Coding
- c.6828C>T
- MANE Select
- NM_001142800
- dbSNP
- rs373606872
- Type
- single nucleotide variant
- Location
- chr6:63999081 (GRCh38)
- Gene constraint
- LOEUF 0.96 · pLI <0.01 (gnomAD)
- Residue 2276
- the laminin g-like 2 domain
Similar variants
- EYS p.Ala2276Val Uncertain significance ★ ⚠ same residue
- EYS p.Ala2276fs Likely pathogenic ★ same residue
- EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same type
- EYS c.1056+3A>C Likely pathogenic ★★ same type
- EYS c.1057-1G>A Likely pathogenic ★★ same type
- EYS c.1184+1G>A Pathogenic/Likely pathogenic ★★ same type
- EYS c.1184+1G>T Likely pathogenic ★★ same type
- EYS c.1185-1G>A Likely pathogenic ★★ 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/eys-p-ala2276 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown