Is EHD3 p.Arg344Trp (c.1030C>T) pathogenic?

EHD3 p.Arg344Trp (c.1030C>T) is classified Uncertain significance in EHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: ambiguous (0.3597); Very rare (popmax 0.00195%, nfe).

How common is EHD3 p.Arg344Trp (c.1030C>T) in the general population?

EHD3 p.Arg344Trp (c.1030C>T) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about EHD3 p.Arg344Trp (c.1030C>T)?

AlphaMissense predicts ambiguous (score 0.3597) — an in-silico prediction, not a clinical call.

EHD3 p.Arg344Trp

c.1030C>T · rs1028760156 · VCV3087771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3597	ambiguous
REVEL	0.403	indeterminate
SaProt	LLR -13.69	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.85	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,876 bp · p 0.16 · regional, not allelic
Overall
CADD	25.4	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 0.00195% European (non-Finnish) · 23/1,180,024 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00171% 25/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00195%	51,305
Remaining individualsnot grpmax-eligible	0.0016%	62,510
African / African-American	0.00133%	75,056

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.Arg344Trp
Coding: c.1030C>T
MANE Select: NM_014600
dbSNP: rs1028760156
Type: single nucleotide variant
Location: chr2:31261663 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI 0.61 (gnomAD)
Structure: AlphaFold pLDDT 88.56

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-arg344trp (accessed [today's date]).

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