Is ERF p.Lys401fs (c.1201_1202del) pathogenic?

ERF p.Lys401fs (c.12011202del) is classified Pathogenic/Likely pathogenic in ERF (ClinVar, Multiple submitters, 19 submitters; last evaluated 2025-07-07). Very rare (popmax 0.000254%, nfe); Associated with Noonan-like syndrome.

What condition is associated with ERF p.Lys401fs (c.1201_1202del)?

ERF p.Lys401fs (c.1201_1202del) is associated with Noonan-like syndrome, TWIST1-related craniosynostosis, craniosynostosis 4 (ClinVar).

How common is ERF p.Lys401fs (c.1201_1202del) in the general population?

ERF p.Lys401fs (c.1201_1202del) is very rare (popmax 0.000254%, nfe) (gnomAD).

ERF p.Lys401fs

c.1201_1202del · rs1064794325 · VCV420168

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Noonan-like 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	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 · substitutions only
Constraint at this position
Conservation	phyloP 0.3	GERP -1.1, phastCons 0.024

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,598 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000206% 3/1,455,378 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ERF
Protein: p.Lys401fs
Coding: c.1201_1202del
MANE Select: NM_006494
dbSNP: rs1064794325
Type: Deletion
Location: chr19:42248910 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 401: the 'disordered' region

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

Disease context

Noonan-like syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: TWIST1-related craniosynostosis craniosynostosis 4 Chitayat syndrome Noonan syndrome neurodevelopmental disorder

Similar variants

ERF p.Lys401Glu Uncertain significance ★★ ⚠ same residue
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.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-lys401fs (accessed [today's date]).

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