EVC2 p.Thr699=
c.2097G>A · rs556009947 · VCV2922924
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0121%, sas)
Conditions
2
acrofacial dysostosis, Weyers type
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -3.8 |
| Overall | ||
| CADD | 0.018 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0121%
South Asian · 11/91,074 alleles
Filtering AF
0.00676%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00522%
Overall
0.00229%
37/1,614,106 alleles · ultra-rare
exomes 34/1,461,820 · genomes 3/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0121% | 8,279 |
| East Asian | 0.00892% | 11,216 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| European (non-Finnish) | 0.00169% | 59,000 |
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
- EVC2
- Protein
- p.Thr699=
- Coding
- c.2097G>A
- MANE Select
- NM_147127
- dbSNP
- rs556009947
- Type
- single nucleotide variant
- Location
- chr4:5622941 (GRCh38)
- Gene constraint
- LOEUF 1.092 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.33
- Residue 699
- a UniProt-annotated variant site (in)
Similar variants
- EVC2 p.Thr699Met Uncertain significance ★★ ⚠ same residue
- EVC2 p.Thr699Ala Benign/Likely benign ★★ same residue
- EVC2 p.Thr699Val Uncertain significance ★★ same residue
- EVC2 c.2046+1G>A Likely pathogenic ★★ same condition
- EVC2 c.2047-2A>G Likely pathogenic ★★ same condition
- EVC2 c.229-1G>T Likely pathogenic ★★ same condition
- EVC2 c.229-2A>G Likely pathogenic ★★ same condition
- EVC2 c.3360+1G>A Pathogenic ★★ 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/evc2-p-thr699 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown