Is EHD1 p.Val100Ile (c.298G>A) pathogenic?

EHD1 p.Val100Ile (c.298G>A) is classified Uncertain significance in EHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1009); Absent from gnomAD v4.1.

How common is EHD1 p.Val100Ile (c.298G>A) in the general population?

EHD1 p.Val100Ile (c.298G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EHD1 p.Val100Ile (c.298G>A)?

AlphaMissense predicts likely benign (score 0.1009) — an in-silico prediction, not a clinical call.

EHD1 p.Val100Ile

c.298G>A · VCV4016959

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1009 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1009	likely benign
REVEL	0.435	indeterminate
SaProt	LLR -8.19	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 7.4	GERP -0.32, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 24 kb · p 2.1e-14 · regional, not allelic
Overall
CADD	24.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EHD1
Protein: p.Val100Ile
Coding: c.298G>A
MANE Select: NM_006795
Type: single nucleotide variant
Location: chr11:64878167 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 89.65 · 5 PDB
Residue 100: the dynamin-type g domain

Full EHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EHD1 p.Ala273= Benign ★★ same type
EHD1 p.Gly464= Benign ★★ same type
EHD1 p.Leu114= Benign ★★ same type
EHD1 p.Leu187= Benign ★★ same type
EHD1 p.Ala304Gly Uncertain significance ★ ⚠ same type
EHD1 p.Ala308Thr Uncertain significance ★ ⚠ same type
EHD1 p.Ala373Val Uncertain significance ★ ⚠ same type
EHD1 p.Ala413Val 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/ehd1-p-val100ile (accessed [today's date]).

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