Is EHD3 p.Arg231Gln (c.692G>A) pathogenic?

EHD3 p.Arg231Gln (c.692G>A) is classified Uncertain significance in EHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely pathogenic (0.987); Very rare (popmax 0.00891%, eas).

How common is EHD3 p.Arg231Gln (c.692G>A) in the general population?

EHD3 p.Arg231Gln (c.692G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about EHD3 p.Arg231Gln (c.692G>A)?

AlphaMissense predicts likely pathogenic (score 0.987) — an in-silico prediction, not a clinical call.

EHD3 p.Arg231Gln

c.692G>A · VCV4663511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.987	likely pathogenic
REVEL	0.902	moderately pathogenic-leaning
SaProt	LLR -14.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 129 bp · p 4.4e-05 · regional, not allelic
Overall
CADD	34.0	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 0.00891% East Asian · 4/44,886 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000889% 13/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,222
African / African-American	0.00133%	75,062
European (non-Finnish)	0.000678%	147,504

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: EHD3
Protein: p.Arg231Gln
Coding: c.692G>A
MANE Select: NM_014600
Type: single nucleotide variant
Location: chr2:31260699 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI 0.61 (gnomAD)
Structure: AlphaFold pLDDT 88.56
Residue 231: the dynamin-type g domain

Full EHD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EHD3 c.502+9C>T Benign ★★ same type
EHD3 p.Arg215= Benign ★★ same type
EHD3 p.Ala127Thr Uncertain significance ★ ⚠ same type
EHD3 p.Ala131Thr Uncertain significance ★ ⚠ same type
EHD3 p.Ala290Val Uncertain significance ★ ⚠ same type
EHD3 p.Ala413Ser Uncertain significance ★ ⚠ same type
EHD3 p.Ala437Thr Uncertain significance ★ ⚠ same type
EHD3 p.Ala99Val 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/ehd3-p-arg231gln (accessed [today's date]).

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