EFNB1 p.Pro119Ala
c.355C>G · VCV3724253
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9903 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9903 | likely pathogenic ✓ concordant with ClinVar |
|---|---|---|
| REVEL | 0.94 | strongly pathogenic-leaning |
| SaProt | LLR -13.46 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.1, phastCons 1 |
| Regional constraint | o/e 0.73 | unconstrained · MANE · 11 kb · p 3.3e-06 · regional, not allelic |
| Overall | ||
| CADD | 24.5 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- EFNB1
- Protein
- p.Pro119Ala
- Coding
- c.355C>G
- MANE Select
- NM_004429
- Type
- single nucleotide variant
- Location
- chrX:68838843 (GRCh38)
- Structure
- AlphaFold pLDDT 71.68 · 1 PDB
- Residue 119
- a disulfide bond; a UniProt-annotated variant site (in cfns); the ephrin rbd domain
Similar variants
- EFNB1 p.Pro119Thr Uncertain significance ★ ⚠ same residue
- EFNB1 c.128+1G>C Likely pathogenic ★★ same type
- EFNB1 c.499+1G>A Pathogenic/Likely pathogenic ★★ same type
- EFNB1 p.Arg66Ter Pathogenic ★★ same type
- EFNB1 p.Gln175Ter Likely pathogenic ★★ same type
- EFNB1 p.Gln85Ter Pathogenic ★★ same type
- EFNB1 p.Gly10= Pathogenic ★★ same type
- EFNB1 p.Gly151Ser Pathogenic ★★ 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/efnb1-p-pro119ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown