Is ERF p.Arg233Gln (c.698G>A) pathogenic?

ERF p.Arg233Gln (c.698G>A) is classified Uncertain significance in ERF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-20). AlphaMissense: likely benign (0.1651); Very rare (popmax 0.00228%, sas); Associated with Inborn genetic diseases.

What condition is associated with ERF p.Arg233Gln (c.698G>A)?

ERF p.Arg233Gln (c.698G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ERF p.Arg233Gln (c.698G>A) in the general population?

ERF p.Arg233Gln (c.698G>A) is very rare (popmax 0.00228%, sas) (gnomAD).

What do computational predictors say about ERF p.Arg233Gln (c.698G>A)?

AlphaMissense predicts likely benign (score 0.1651) — an in-silico prediction, not a clinical call.

ERF p.Arg233Gln

c.698G>A · rs754586626 · VCV2251480

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00228%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1651	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.48, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,421 bp · p 0.024 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00228% South Asian · 2/87,690 alleles

Filtering AF 0.000697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000545%

Overall 0.00112% 16/1,431,836 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00228%	43,845
European (non-Finnish)	0.0012%	83,257

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.Arg233Gln
Coding: c.698G>A
MANE Select: NM_006494
dbSNP: rs754586626
Type: single nucleotide variant
Location: chr19:42249414 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERF p.Arg233Ter Pathogenic ★★ same residue
ERF p.Gln263Ter Pathogenic ★★ same condition
ERF p.Ala462Pro Uncertain significance ★★ ⚠ same condition
ERF p.Arg179His Uncertain significance ★★ ⚠ same condition
ERF p.Arg312Gln Uncertain significance ★★ ⚠ same condition
ERF p.Arg546Ter Uncertain significance ★★ same condition
ERF p.Lys401Glu Uncertain significance ★★ ⚠ same condition
ERF p.Val128Gly 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-arg233gln (accessed [today's date]).

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