Is EFNB1 p.Arg66fs (c.196del) pathogenic?

EFNB1 p.Arg66fs (c.196del) is classified Pathogenic in EFNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-09). Absent from gnomAD; Associated with craniofrontonasal syndrome.

What condition is associated with EFNB1 p.Arg66fs (c.196del)?

EFNB1 p.Arg66fs (c.196del) is associated with craniofrontonasal syndrome (ClinVar).

How common is EFNB1 p.Arg66fs (c.196del) in the general population?

EFNB1 p.Arg66fs (c.196del) is absent from gnomAD (gnomAD).

EFNB1 p.Arg66fs

c.196del · rs2520012797 · VCV1895436

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

craniofrontonasal syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EFNB1
Protein: p.Arg66fs
Coding: c.196del
MANE Select: NM_004429
dbSNP: rs2520012797
Type: Deletion
Location: chrX:68838680 (GRCh38)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 66: a disulfide bond; 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.Arg66Ter Pathogenic ★★ same residue
EFNB1 p.Pro34fs Pathogenic/Likely pathogenic ★★ same condition
EFNB1 c.499+2_499+7del Likely pathogenic ★ same condition
EFNB1 p.Arg23fs Likely pathogenic ★ same condition
EFNB1 p.Asn187fs Pathogenic ★ same condition
EFNB1 p.Ile112fs Likely pathogenic ★ same condition
EFNB1 p.Lys48fs Pathogenic ★ same condition
EFNB1 p.Arg66Gln Uncertain significance ★ ⚠ same residue

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-arg66fs (accessed [today's date]).

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