ENG p.Pro131=
c.393G>C · VCV3508500
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, sas)
Conditions
1
Cardiovascular phenotype
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 -2.9 | GERP -4.1 |
| Overall | ||
| CADD | 0.145 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
South Asian · 15/91,068 alleles
Filtering AF
0.0101%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.000929%
15/1,613,958 alleles · ultra-rare
exomes 15/1,461,746 · genomes 0/152,212 · joint denominator
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
- ENG
- Protein
- p.Pro131=
- Coding
- c.393G>C
- MANE Select
- NM_001114753
- Type
- single nucleotide variant
- Location
- chr9:127826640 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84 · 3 PDB
- Residue 131
- the 'required for interaction with gdf2' region; the 'or2' region
Similar variants
- ENG p.Pro131Ala Uncertain significance ★ ⚠ same residue
- ENG p.Pro131fs Pathogenic ★★ same residue
- ENG p.Pro131Leu Benign ★★★ same residue
- ENG p.Pro131Gln Likely benign ★ same residue
- ENG c.1134+1G>T Pathogenic/Likely pathogenic ★★ same condition
- ENG c.1311+2T>A Pathogenic ★★ same condition
- ENG c.1428+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ENG c.1687-1G>A Pathogenic/Likely 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/eng-p-pro131 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown