Is EHF p.Arg232Gln (c.695G>A) pathogenic?

EHF p.Arg232Gln (c.695G>A) is classified Uncertain significance in EHF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: ambiguous (0.4102); Very rare (popmax 0.00186%, nfe).

How common is EHF p.Arg232Gln (c.695G>A) in the general population?

EHF p.Arg232Gln (c.695G>A) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about EHF p.Arg232Gln (c.695G>A)?

AlphaMissense predicts ambiguous (score 0.4102) — an in-silico prediction, not a clinical call.

EHF p.Arg232Gln

c.695G>A · VCV4247559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4102	ambiguous
REVEL	0.422	indeterminate
SaProt	LLR -8.92	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 1,873 bp · p 8e-07 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,179,756 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,613,720 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: EHF
Protein: p.Arg232Gln
Coding: c.695G>A
MANE Select: NM_012153
Type: single nucleotide variant
Location: chr11:34658620 (GRCh38)
Gene constraint: LOEUF 0.483 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 69.12 · 1 PDB
Residue 232: a DNA-binding region

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

Similar variants

EHF p.Val128= Benign ★★ same type
EHF c.-3-10022G>T Uncertain significance ★ same type
EHF c.-3-9995T>C Uncertain significance ★ same type
EHF p.Arg168Gln Uncertain significance ★ ⚠ same type
EHF p.Arg168Gly Uncertain significance ★ same type
EHF p.Arg214His Uncertain significance ★ ⚠ same type
EHF p.Arg293Gln Uncertain significance ★ ⚠ same type
EHF p.Arg293Leu Uncertain significance ★ ⚠ 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/ehf-p-arg232gln (accessed [today's date]).

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