Is EFNB1 p.Arg154Pro (c.461G>C) pathogenic?

EFNB1 p.Arg154Pro (c.461G>C) is classified Uncertain significance in EFNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-19). AlphaMissense: likely pathogenic (0.8402); Absent from gnomAD v4.1.

How common is EFNB1 p.Arg154Pro (c.461G>C) in the general population?

EFNB1 p.Arg154Pro (c.461G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFNB1 p.Arg154Pro (c.461G>C)?

AlphaMissense predicts likely pathogenic (score 0.8402) — an in-silico prediction, not a clinical call.

EFNB1 p.Arg154Pro

c.461G>C · rs146636295 · VCV1710646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8402 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8402	likely pathogenic
REVEL	0.577	indeterminate
SaProt	LLR -9.60	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -1.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 11 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	22.4	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.Arg154Pro
Coding: c.461G>C
MANE Select: NM_004429
dbSNP: rs146636295
Type: single nucleotide variant
Location: chrX:68839718 (GRCh38)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 154: a UniProt-annotated variant site (in); the ephrin rbd domain

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

Similar variants

EFNB1 p.Arg154His Likely benign ★★ same residue
EFNB1 p.Arg154fs Likely pathogenic ★ 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

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-arg154pro (accessed [today's date]).

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