Is ERF p.Arg101Trp (c.301C>T) pathogenic?

ERF p.Arg101Trp (c.301C>T) is classified Uncertain significance in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely pathogenic (0.9995); Very rare (popmax 8.47e-05%, nfe).

How common is ERF p.Arg101Trp (c.301C>T) in the general population?

ERF p.Arg101Trp (c.301C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ERF p.Arg101Trp (c.301C>T)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

ERF p.Arg101Trp

c.301C>T · rs769239795 · VCV3252220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 5% in ERF
REVEL	0.4	indeterminate
SaProt	LLR -11.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -2.2, phastCons 0.94
Regional constraint	o/e 0.22	constrained · MANE · 558 bp · p 2.8e-12 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 6.84e-05% 1/1,461,880 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.Arg101Trp
Coding: c.301C>T
MANE Select: NM_006494
dbSNP: rs769239795
Type: single nucleotide variant
Location: chr19:42249899 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 101: a DNA-binding region

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

Similar variants

ERF p.Arg183Ter Pathogenic ★★ same type
ERF p.Arg207Ter Pathogenic/Likely pathogenic ★★ same type
ERF p.Arg218Ter Pathogenic/Likely pathogenic ★★ same type
ERF p.Arg233Ter Pathogenic ★★ same type
ERF p.Arg86Cys Pathogenic/Likely pathogenic ★★ same type
ERF p.Gln263Ter Pathogenic ★★ same type
ERF p.Gly53Arg Likely pathogenic ★★ same type
ERF p.Ser24Ter Pathogenic/Likely 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-arg101trp (accessed [today's date]).

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