Is ERF p.Trp14Ter (c.41G>A) pathogenic?

ERF p.Trp14Ter (c.41G>A) is classified Likely pathogenic in ERF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-01). Absent from gnomAD v4.1; Associated with Lambdoidal craniosynostosis.

What condition is associated with ERF p.Trp14Ter (c.41G>A)?

ERF p.Trp14Ter (c.41G>A) is associated with Lambdoidal craniosynostosis (ClinVar).

How common is ERF p.Trp14Ter (c.41G>A) in the general population?

ERF p.Trp14Ter (c.41G>A) is absent from gnomAD v4.1 (gnomAD).

ERF p.Trp14Ter

c.41G>A · rs2036427390 · VCV1031051

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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	predicted	premature termination codon in exon 2 of 4
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Overall
CADD	43.0	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.Trp14Ter
Coding: c.41G>A
MANE Select: NM_006494
dbSNP: rs2036427390
Type: single nucleotide variant
Location: chr19:42250547 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB

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.Trp14Gly Uncertain significance ★ ⚠ same residue
ERF p.Ser24Ter Pathogenic/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-trp14ter (accessed [today's date]).

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