Is EFNB1 p.Met158Val (c.472A>G) pathogenic?

EFNB1 p.Met158Val (c.472A>G) is classified Pathogenic/Likely pathogenic in EFNB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.9612); Absent from gnomAD v4.1; Associated with craniofrontonasal syndrome.

What condition is associated with EFNB1 p.Met158Val (c.472A>G)?

EFNB1 p.Met158Val (c.472A>G) is associated with craniofrontonasal syndrome (ClinVar).

How common is EFNB1 p.Met158Val (c.472A>G) in the general population?

EFNB1 p.Met158Val (c.472A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFNB1 p.Met158Val (c.472A>G)?

AlphaMissense predicts likely pathogenic (score 0.9612) — an in-silico prediction, not a clinical call.

EFNB1 p.Met158Val

c.472A>G · rs28936071 · VCV11711

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9612 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

craniofrontonasal syndrome

Computational evidence

Protein change
AlphaMissense	0.9612	likely pathogenic ✓ concordant with ClinVar
REVEL	0.868	moderately pathogenic-leaning
SaProt	LLR -10.86	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 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 11 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	23.5	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.Met158Val
Coding: c.472A>G
MANE Select: NM_004429
dbSNP: rs28936071
Type: single nucleotide variant
Location: chrX:68839729 (GRCh38)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 158: a UniProt-annotated variant site (in cfns); the ephrin rbd domain

Full EFNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

craniofrontonasal syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFNB1 p.Met158Arg Likely pathogenic ★ same residue
EFNB1 p.Met158Ile Pathogenic same residue
EFNB1 c.128+1G>C Likely pathogenic ★★ same condition
EFNB1 c.499+1G>A Pathogenic/Likely pathogenic ★★ same condition
EFNB1 p.Arg66Ter Pathogenic ★★ same condition
EFNB1 p.Gln175Ter Likely pathogenic ★★ same condition
EFNB1 p.Gln85Ter Pathogenic ★★ same condition
EFNB1 p.Gly151Ser 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/efnb1-p-met158val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown