ECE2 p.Val248=
c.744T>C · rs76939864 · VCV780899
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.95%, 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 -0.66 | GERP -3.8, phastCons 0.024 |
| Overall | ||
| CADD | 4.794 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.95%
African / African-American · 2,959/74,998 alleles
Filtering AF
3.83%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.78%
Overall
0.202%
3,256/1,613,942 alleles · low-frequency
exomes 1,628/1,461,708 · genomes 1,628/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.95% | 25 |
| Remaining individualsnot grpmax-eligible | 0.235% | 425 |
| Admixed American | 0.172% | 582 |
| Middle Eastern | 0.132% | 758 |
| South Asian | 0.0132% | 7,587 |
| European (non-Finnish) | 0.00229% | 43,702 |
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
- ECE2
- Protein
- p.Val248=
- Coding
- c.744T>C
- MANE Select
- NM_001100121
- dbSNP
- rs76939864
- Type
- single nucleotide variant
- Location
- chr3:184278307 (GRCh38)
- Gene constraint
- LOEUF 0.965 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.75
- Residue 248
- the peptidase m13 domain
Similar variants
- ECE2 p.Arg453Gln Benign ★★ same type
- ECE2 p.Ser400= Benign ★★ same type
- EEF1AKMT4-ECE2 p.Val127Ala Benign ★★ same type
- ECE2 p.Ala338Val Uncertain significance ★ ⚠ same type
- ECE2 p.Ala437Thr Uncertain significance ★ ⚠ same type
- ECE2 p.Ala575Thr Uncertain significance ★ ⚠ same type
- ECE2 p.Ala638Gly Uncertain significance ★ ⚠ same type
- ECE2 p.Ala72Val 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/ece2-p-val248 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown