Is EFNB1 p.Ile250Ser (c.749T>G) pathogenic?

EFNB1 p.Ile250Ser (c.749T>G) is classified Uncertain significance in EFNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely pathogenic (0.8985); Absent from gnomAD v4.1; Associated with craniofrontonasal syndrome.

What condition is associated with EFNB1 p.Ile250Ser (c.749T>G)?

EFNB1 p.Ile250Ser (c.749T>G) is associated with craniofrontonasal syndrome (ClinVar).

How common is EFNB1 p.Ile250Ser (c.749T>G) in the general population?

EFNB1 p.Ile250Ser (c.749T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFNB1 p.Ile250Ser (c.749T>G)?

AlphaMissense predicts likely pathogenic (score 0.8985) — an in-silico prediction, not a clinical call.

EFNB1 p.Ile250Ser

c.749T>G · rs1569398326 · VCV634590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

craniofrontonasal syndrome

Computational evidence

Protein change
AlphaMissense	0.8985	likely pathogenic
REVEL	0.875	moderately pathogenic-leaning
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 11 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	24.4	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.Ile250Ser
Coding: c.749T>G
MANE Select: NM_004429
dbSNP: rs1569398326
Type: single nucleotide variant
Location: chrX:68840362 (GRCh38)
Structure: AlphaFold pLDDT 71.68 · 1 PDB

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.Ile250Met Uncertain significance ★ ⚠ 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
EFNB1 p.Met158Val Pathogenic/Likely 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-ile250ser (accessed [today's date]).

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