Is EHF p.Arg293Gln (c.878G>A) pathogenic?

EHF p.Arg293Gln (c.878G>A) is classified Uncertain significance in EHF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely benign (0.188); Very rare (popmax 0.00501%, amr).

How common is EHF p.Arg293Gln (c.878G>A) in the general population?

EHF p.Arg293Gln (c.878G>A) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about EHF p.Arg293Gln (c.878G>A)?

AlphaMissense predicts likely benign (score 0.188) — an in-silico prediction, not a clinical call.

EHF p.Arg293Gln

c.878G>A · VCV3507422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.188	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -4.48	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 10	GERP 2.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 93 bp · p 0.14 · regional, not allelic
Overall
CADD	24.3	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 0.00501% Admixed American · 3/59,858 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.00118% 19/1,612,974 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,953
South Asian	0.0044%	22,738
African / African-American	0.00134%	74,818
European (non-Finnish)	0.000933%	107,234

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.Arg293Gln
Coding: c.878G>A
MANE Select: NM_012153
Type: single nucleotide variant
Location: chr11:34658906 (GRCh38)
Gene constraint: LOEUF 0.483 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 69.12 · 1 PDB

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

Similar variants

EHF p.Arg293Leu Uncertain significance ★ ⚠ same residue
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.Arg232Gln 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-arg293gln (accessed [today's date]).

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