ECE2 p.Thr434=
c.1302G>A · rs781718047 · VCV2654313
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00878%, sas)
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 -11 | GERP -3.5 |
| Overall | ||
| CADD | 0.868 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00878%
South Asian · 8/91,090 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.00211%
34/1,614,074 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00878% | 11,386 |
| East Asian | 0.00445% | 22,450 |
| European (non-Finnish) | 0.00186% | 53,638 |
| Admixed American | 0.00167% | 60,004 |
| African / African-American | 0.00133% | 74,940 |
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.Thr434=
- Coding
- c.1302G>A
- MANE Select
- NM_001100121
- dbSNP
- rs781718047
- Type
- single nucleotide variant
- Location
- chr3:184287875 (GRCh38)
- Gene constraint
- LOEUF 0.965 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.75
- Residue 434
- a disulfide bond; the peptidase m13 domain
Similar variants
- ECE2 p.Arg453Gln Benign ★★ same type
- ECE2 p.Ser400= Benign ★★ same type
- ECE2 p.Val248= 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
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-thr434 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown