Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 47.7%, mid) — too common for a highly-penetrant pathogenic allele
Conditions
1
cataract 6 multiple types
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 -0.15 | GERP -2.6, phastCons 0.08 |
| Overall | ||
| CADD | 6.063 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
47.7%
Middle Eastern · 2,888/6,060 alleles
Filtering AF
46.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 45.6%
Overall
39.2%
631,326/1,608,510 alleles · common
exomes 573,757/1,456,402 · genomes 57,569/152,108 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 47.7% | 2 |
| Amishnot grpmax-eligible | 47.1% | 2 |
| South Asian | 45.9% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 45.1% | 2 |
| European (non-Finnish) | 40.2% | 2 |
| Remaining individualsnot grpmax-eligible | 39.5% | 3 |
| Admixed American | 37.2% | 3 |
| African / African-American | 35.4% | 3 |
| Finnishnot grpmax-eligible | 34.2% | 3 |
| East Asian | 11.1% | 9 |
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
- EPHA2
- Protein
- p.Pro329=
- Coding
- c.987C>T
- MANE Select
- NM_004431
- dbSNP
- rs2230597
- Type
- single nucleotide variant
- Location
- chr1:16138178 (GRCh38)
- Gene constraint
- LOEUF 0.652 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.73 · 103 PDB
- Residue 329
- the fibronectin type-iii 1 domain; an α-helix
Disease context
cataract 6 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Early onset non-syndromic cataract (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive, X-linked recessive
- Onset
- Infancy, Neonatal
Similar variants
- EPHA2 p.Pro329Ser Uncertain significance ★ ⚠ same residue
- EPHA2 c.2826-9G>A Pathogenic ★★ same condition
- EPHA2 p.Ala321Val Uncertain significance ★★ ⚠ same condition
- EPHA2 p.Arg175His Uncertain significance ★★ ⚠ same condition
- EPHA2 p.Arg195Cys Uncertain significance ★★ ⚠ same condition
- EPHA2 p.Arg315Trp Uncertain significance ★★ ⚠ same condition
- EPHA2 p.Arg428His Uncertain significance ★★ ⚠ same condition
- EPHA2 p.Arg560His Uncertain significance ★★ ⚠ same condition
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/epha2-p-pro329 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown