Is EHD2 p.Val100Ile (c.298G>A) pathogenic?

EHD2 p.Val100Ile (c.298G>A) is classified Uncertain significance in EHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.0655); Very rare (popmax 0.00432%, nfe).

How common is EHD2 p.Val100Ile (c.298G>A) in the general population?

EHD2 p.Val100Ile (c.298G>A) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about EHD2 p.Val100Ile (c.298G>A)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

EHD2 p.Val100Ile

c.298G>A · rs778830768 · VCV3087767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.45	indeterminate
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 5.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 25 kb · p 0.00029 · regional, not allelic
Overall
CADD	23.4	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 0.00432% European (non-Finnish) · 51/1,179,940 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00366% 59/1,611,714 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,136
Admixed American	0.00333%	29,990
Finnishnot grpmax-eligible	0.00323%	30,934
Remaining individualsnot grpmax-eligible	0.0032%	31,232
African / African-American	0.00133%	74,932
South Asian	0.0011%	91,076

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.Val100Ile
Coding: c.298G>A
MANE Select: NM_014601
dbSNP: rs778830768
Type: single nucleotide variant
Location: chr19:47716910 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.15
Residue 100: the dynamin-type g domain

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-val100ile (accessed [today's date]).

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