Is ERF p.Phe504fs (c.1509del) pathogenic?

ERF p.Phe504fs (c.1509del) is classified Pathogenic in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). Absent from gnomAD; Associated with Noonan Syndrome-like developmental disorder.

What condition is associated with ERF p.Phe504fs (c.1509del)?

ERF p.Phe504fs (c.1509del) is associated with Noonan Syndrome-like developmental disorder (ClinVar).

How common is ERF p.Phe504fs (c.1509del) in the general population?

ERF p.Phe504fs (c.1509del) is absent from gnomAD (gnomAD).

ERF p.Phe504fs

c.1509del · rs2513517350 · VCV2684000

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

Noonan Syndrome-like developmental disorder

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 2.3	GERP -2.6, phastCons 1

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.Phe504fs
Coding: c.1509del
MANE Select: NM_006494
dbSNP: rs2513517350
Type: Deletion
Location: chr19:42248603 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 504: the 'disordered' region

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

Disease context

Noonan Syndrome-like developmental disorder

Similar variants

ERF p.Asp6fs Likely pathogenic ★ same condition
ERF p.Pro4fs Pathogenic ★ same condition
ERF p.Glu516fs Uncertain significance ★ same condition
ERF p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg218Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg233Ter Pathogenic ★★ same condition
ERF p.Arg86Cys Pathogenic/Likely pathogenic ★★ same condition
ERF p.Gly53Arg 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-phe504fs (accessed [today's date]).

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