Is EFNB1 p.Phe234Leu (c.702C>A) pathogenic?

EFNB1 p.Phe234Leu (c.702C>A) is classified Uncertain significance in EFNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: ambiguous (0.4878); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EFNB1 p.Phe234Leu (c.702C>A)?

EFNB1 p.Phe234Leu (c.702C>A) is associated with Inborn genetic diseases (ClinVar).

How common is EFNB1 p.Phe234Leu (c.702C>A) in the general population?

EFNB1 p.Phe234Leu (c.702C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFNB1 p.Phe234Leu (c.702C>A)?

AlphaMissense predicts ambiguous (score 0.4878) — an in-silico prediction, not a clinical call.

EFNB1 p.Phe234Leu

c.702C>A · VCV3843689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4878 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4878	ambiguous
REVEL	0.38	indeterminate
SaProt	LLR -7.39	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.61	GERP -1.3, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 11 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	14.04	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.Phe234Leu
Coding: c.702C>A
MANE Select: NM_004429
Type: single nucleotide variant
Location: chrX:68840315 (GRCh38)
Structure: AlphaFold pLDDT 71.68 · 1 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFNB1 p.Ala242Val Uncertain significance ★★ ⚠ same condition
EFNB1 p.Ala340Val Uncertain significance ★★ ⚠ same condition
EFNB1 p.Arg180Ser Uncertain significance ★★ ⚠ same condition
EFNB1 p.Arg199Trp Uncertain significance ★★ ⚠ same condition
EFNB1 p.Arg307Gln Uncertain significance ★★ ⚠ same condition
EFNB1 p.Asp206His Uncertain significance ★★ ⚠ same condition
EFNB1 p.His272Tyr Uncertain significance ★★ ⚠ same condition
EFNB1 p.Leu24Phe Uncertain significance ★★ ⚠ 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-phe234leu (accessed [today's date]).

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