Is ERF p.Leu85fs (c.253del) pathogenic?

ERF p.Leu85fs (c.253del) is classified Pathogenic in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). Associated with TWIST1-related craniosynostosis.

What condition is associated with ERF p.Leu85fs (c.253del)?

ERF p.Leu85fs (c.253del) is associated with TWIST1-related craniosynostosis (ClinVar).

ERF p.Leu85fs

c.253del · VCV3686735

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 2 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: ERF
Protein: p.Leu85fs
Coding: c.253del
MANE Select: NM_006494
Type: Deletion
Location: chr19:42250335 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 85: a DNA-binding region; an α-helix

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.Arg143fs Pathogenic/Likely pathogenic ★★ same condition
ERF p.Asp188_Cys189insTer Pathogenic ★★ same condition
ERF p.Gly299fs Pathogenic/Likely pathogenic ★★ same condition
ERF p.Lys401fs Pathogenic/Likely pathogenic ★★ same condition
ERF p.Pro358fs Pathogenic/Likely pathogenic ★★ same condition
ERF p.Ser304del Pathogenic ★★ same condition
ERF c.-44_22+11del Pathogenic ★ same condition
ERF p.Gln341fs 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-leu85fs (accessed [today's date]).

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