EPC2 p.Arg253=
c.759A>G · rs35674266 · VCV783121
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.02%, afr)
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 4.2 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 10.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.02%
African / African-American · 1,502/74,238 alleles
Filtering AF
1.94%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9%
Overall
0.114%
1,821/1,598,680 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.02% | 49 |
| Middle Eastern | 0.348% | 287 |
| Admixed American | 0.189% | 528 |
| Remaining individualsnot grpmax-eligible | 0.134% | 746 |
| European (non-Finnish) | 0.00868% | 11,517 |
| South Asian | 0.00461% | 21,676 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00342% | 29,280 |
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
- EPC2
- Protein
- p.Arg253=
- Coding
- c.759A>G
- MANE Select
- NM_015630
- dbSNP
- rs35674266
- Type
- single nucleotide variant
- Location
- chr2:148761874 (GRCh38)
- Gene constraint
- LOEUF 0.203 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 58.35
Similar variants
- EPC2 c.666+9C>T Benign ★★ same type
- EPC2 p.Phe6= Benign ★★ same type
- EPC2 p.Ser611= Benign ★★ same type
- EPC2 p.Ala13Thr Uncertain significance ★ ⚠ same type
- EPC2 p.Ala14Asp Uncertain significance ★ ⚠ same type
- EPC2 p.Ala634Thr Uncertain significance ★ ⚠ same type
- EPC2 p.Ala711Thr Uncertain significance ★ ⚠ same type
- EPC2 p.Ala711Val 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/epc2-p-arg253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown