Is ERF p.Pro133fs (c.397_407del) pathogenic?

ERF p.Pro133fs (c.397407del) is classified Likely pathogenic in ERF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-02). Absent from gnomAD.

How common is ERF p.Pro133fs (c.397_407del) in the general population?

ERF p.Pro133fs (c.397_407del) is absent from gnomAD (gnomAD).

ERF p.Pro133fs

c.397_407del · rs1568472223 · VCV593753

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 -11	GERP -3.7

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.Pro133fs
Coding: c.397_407del
MANE Select: NM_006494
dbSNP: rs1568472223
Type: Deletion
Location: chr19:42249705 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 133: the 'disordered' region

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

Similar variants

ERF p.Pro133Leu Uncertain significance ★★ ⚠ same residue
ERF p.Pro133= Likely benign same residue
ERF p.Arg143fs Pathogenic/Likely pathogenic ★★ same type
ERF p.Asp188_Cys189insTer Pathogenic ★★ same type
ERF p.Gly299fs Pathogenic/Likely pathogenic ★★ same type
ERF p.Lys401fs Pathogenic/Likely pathogenic ★★ same type
ERF p.Pro358fs Pathogenic/Likely pathogenic ★★ same type
ERF p.Ser304del Pathogenic ★★ same type

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-pro133fs (accessed [today's date]).

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