ENTREP1 p.Leu141Phe
c.421C>T · rs116026385 · VCV1179869
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.25%, afr)
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 7.6 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 58 kb · p 0.22 · regional, not allelic |
| Overall | ||
| CADD | 25.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.25%
African / African-American · 918/73,288 alleles
Filtering AF
1.19%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.16%
Overall
0.0642%
1,001/1,558,044 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.25% | 80 |
| Remaining individualsnot grpmax-eligible | 0.0826% | 1,211 |
| Admixed American | 0.0391% | 2,558 |
| Middle Eastern | 0.0169% | 5,918 |
| South Asian | 0.00463% | 21,602 |
| Finnishnot grpmax-eligible | 0.00315% | 31,728 |
| East Asian | 0.00226% | 44,176 |
| European (non-Finnish) | 0.000264% | 379,443 |
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.Leu141Phe
- Coding
- c.421C>T
- MANE Select
- NM_001347995
- dbSNP
- rs116026385
- Type
- single nucleotide variant
- Location
- chr9:69336219 (GRCh38)
- Structure
- AlphaFold pLDDT 60.47
- Residue 141
- the 'mediates interaction with epn1' region
Similar variants
- 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
- ENTREP1 p.Ala574Pro Uncertain significance ★ ⚠ same type
- ENTREP1 p.Ala588Val Conflicting classifications of pathogenicity ★ ⚠ 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-leu141phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown