Is EHD2 p.Arg11Trp (c.31C>T) pathogenic?

EHD2 p.Arg11Trp (c.31C>T) is classified Uncertain significance in EHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.2883); Very rare (popmax 0.00456%, eas).

How common is EHD2 p.Arg11Trp (c.31C>T) in the general population?

EHD2 p.Arg11Trp (c.31C>T) is very rare (popmax 0.00456%, eas) (gnomAD).

What do computational predictors say about EHD2 p.Arg11Trp (c.31C>T)?

AlphaMissense predicts likely benign (score 0.2883) — an in-silico prediction, not a clinical call.

EHD2 p.Arg11Trp

c.31C>T · rs753444147 · VCV2554055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00456%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2883	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -10.67	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 5.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 25 kb · p 0.00029 · regional, not allelic
Overall
CADD	23.5	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 0.00456% East Asian · 2/43,822 alleles

Filtering AF 0.000933% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000459%

Overall 0.00147% 23/1,565,340 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00456%	21,911
South Asian	0.00351%	28,469
Finnishnot grpmax-eligible	0.0034%	29,438
African / African-American	0.00271%	36,884
Admixed American	0.00187%	53,360
Remaining individualsnot grpmax-eligible	0.00166%	60,318
European (non-Finnish)	0.00104%	96,347

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: EHD2
Protein: p.Arg11Trp
Coding: c.31C>T
MANE Select: NM_014601
dbSNP: rs753444147
Type: single nucleotide variant
Location: chr19:47716643 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.15

Full EHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EHD2 p.Ala161Thr Uncertain significance ★ ⚠ same type
EHD2 p.Ala308Thr Uncertain significance ★ ⚠ same type
EHD2 p.Ala340Glu Uncertain significance ★ ⚠ same type
EHD2 p.Ala365Val Uncertain significance ★ ⚠ same type
EHD2 p.Ala391Pro Uncertain significance ★ ⚠ same type
EHD2 p.Ala413Thr Uncertain significance ★ ⚠ same type
EHD2 p.Ala442Asp Uncertain significance ★ ⚠ same type
EHD2 p.Ala461Val 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/ehd2-p-arg11trp (accessed [today's date]).

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