Is ERF p.Gln424Ter (c.1270C>T) pathogenic?

ERF p.Gln424Ter (c.1270C>T) is classified Pathogenic in ERF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-03-01). Absent from gnomAD v4.1; Associated with Lambdoidal craniosynostosis.

What condition is associated with ERF p.Gln424Ter (c.1270C>T)?

ERF p.Gln424Ter (c.1270C>T) is associated with Lambdoidal craniosynostosis (ClinVar).

How common is ERF p.Gln424Ter (c.1270C>T) in the general population?

ERF p.Gln424Ter (c.1270C>T) is absent from gnomAD v4.1 (gnomAD).

ERF p.Gln424Ter

c.1270C>T · rs587777010 · VCV55927

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Lambdoidal craniosynostosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.4, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: ERF
Protein: p.Gln424Ter
Coding: c.1270C>T
MANE Select: NM_006494
dbSNP: rs587777010
Type: single nucleotide variant
Location: chr19:42248842 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 424: the 'disordered' region

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

Disease context

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

Similar variants

ERF p.Ser24Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Trp14Ter Likely pathogenic ★★ same condition
ERF p.Arg180Cys Uncertain significance ★★ ⚠ same condition
ERF p.Gln49Ter Likely pathogenic ★ same condition
ERF p.Gly53Ala Likely pathogenic ★ same condition
ERF c.22+2T>G Conflicting classifications of pathogenicity ★ ⚠ same condition
ERF c.373+8C>T Uncertain significance ★ same condition
ERF p.Arg344Gly 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/erf-p-gln424ter (accessed [today's date]).

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