EFCAB5 p.Val591=
c.1773G>A · rs371953416 · VCV2647620
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, amr)
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 -4.3 | GERP -3.7 |
| Overall | ||
| CADD | 0.409 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
Admixed American · 16/60,008 alleles
Filtering AF
0.0216%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0207%
Overall
0.0199%
321/1,613,950 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0267% | 3,751 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,166 |
| European (non-Finnish) | 0.024% | 4,169 |
| South Asian | 0.00549% | 18,216 |
| African / African-American | 0.00267% | 37,523 |
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
- EFCAB5
- Protein
- p.Val591=
- Coding
- c.1773G>A
- MANE Select
- NM_198529
- dbSNP
- rs371953416
- Type
- single nucleotide variant
- Location
- chr17:30053727 (GRCh38)
- Gene constraint
- LOEUF 0.908 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.22
- Residue 591
- the 'disordered' region
Similar variants
- EFCAB5 p.Ala1262Pro Uncertain significance ★ same type
- EFCAB5 p.Ala128Thr Uncertain significance ★ ⚠ same type
- EFCAB5 p.Ala1493Val Uncertain significance ★ ⚠ same type
- EFCAB5 p.Ala373Val Uncertain significance ★ ⚠ same type
- EFCAB5 p.Ala514Thr Uncertain significance ★ ⚠ same type
- EFCAB5 p.Ala5Pro Uncertain significance ★ ⚠ same type
- EFCAB5 p.Arg1158Gln Uncertain significance ★ ⚠ same type
- EFCAB5 p.Arg1329Gln 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/efcab5-p-val591 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown