ENTREP1 p.Pro475=
c.1425G>A · rs755452769 · VCV514557
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, 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 -7.2 | GERP -3.1 |
| Overall | ||
| CADD | 0.309 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/60,012 alleles
Filtering AF
0.00543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0038%
Overall
0.00192%
31/1,614,058 alleles · ultra-rare
exomes 27/1,461,882 · genomes 4/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,573 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| African / African-American | 0.00267% | 37,461 |
| East Asian | 0.00223% | 44,894 |
| European (non-Finnish) | 0.00161% | 62,107 |
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
- ENTREP1
- Protein
- p.Pro475=
- Coding
- c.1425G>A
- MANE Select
- NM_001347995
- dbSNP
- rs755452769
- Type
- single nucleotide variant
- Location
- chr9:69388267 (GRCh38)
- Structure
- AlphaFold pLDDT 60.47
Similar variants
- ENTREP1 p.Pro475Leu Uncertain significance ★ ⚠ same residue
- ENTREP1 p.Pro475Ser Uncertain significance ★ ⚠ same residue
- ENTREP1 p.Ala374Ser Uncertain significance ★ ⚠ same type
- ENTREP1 p.Ala418Asp Uncertain significance ★ ⚠ same type
- ENTREP1 p.Ala440Ser Uncertain significance ★ ⚠ same type
- ENTREP1 p.Ala440Thr Uncertain significance ★ ⚠ same type
- ENTREP1 p.Ala448Ser Uncertain significance ★ ⚠ same type
- ENTREP1 p.Ala492Val 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/entrep1-p-pro475 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown