Is EFNB1 p.Pro54Arg (c.161C>G) pathogenic?

EFNB1 p.Pro54Arg (c.161C>G) is classified Pathogenic in EFNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-22). AlphaMissense: likely pathogenic (0.998); Absent from gnomAD v4.1.

How common is EFNB1 p.Pro54Arg (c.161C>G) in the general population?

EFNB1 p.Pro54Arg (c.161C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFNB1 p.Pro54Arg (c.161C>G)?

AlphaMissense predicts likely pathogenic (score 0.998) — an in-silico prediction, not a clinical call.

EFNB1 p.Pro54Arg

c.161C>G · rs104894801 · VCV449015

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.998	likely pathogenic ✓ concordant with ClinVar · top 6% in EFNB1
REVEL	0.949	strongly pathogenic-leaning
SaProt	LLR -16.57	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, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 11 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	25.9	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.Pro54Arg
Coding: c.161C>G
MANE Select: NM_004429
dbSNP: rs104894801
Type: single nucleotide variant
Location: chrX:68838649 (GRCh38)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 54: 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

Similar variants

EFNB1 p.Pro54Leu Pathogenic/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
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-pro54arg (accessed [today's date]).

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