Is ERF p.Arg92fs (c.272dup) pathogenic?

ERF p.Arg92fs (c.272dup) is classified Pathogenic in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). Absent from gnomAD; Associated with TWIST1-related craniosynostosis.

What condition is associated with ERF p.Arg92fs (c.272dup)?

ERF p.Arg92fs (c.272dup) is associated with TWIST1-related craniosynostosis (ClinVar).

How common is ERF p.Arg92fs (c.272dup) in the general population?

ERF p.Arg92fs (c.272dup) is absent from gnomAD (gnomAD).

ERF p.Arg92fs

c.272dup · rs2513524258 · VCV2122554

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

TWIST1-related craniosynostosis

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 3 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.2	GERP -3.7, phastCons 0.54

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: ERF
Protein: p.Arg92fs
Coding: c.272dup
MANE Select: NM_006494
dbSNP: rs2513524258
Type: Duplication
Location: chr19:42249927 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 92: a DNA-binding region

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

Disease context

TWIST1-related craniosynostosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERF p.Glu437fs Likely pathogenic ★ same condition
ERF p.Met286fs Pathogenic ★ same condition
ERF p.Arg92= Likely benign ★ same residue
ERF p.Arg143fs Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg183Ter Pathogenic ★★ same condition
ERF p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg218Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg86Cys 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/erf-p-arg92fs (accessed [today's date]).

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