Is EHD2 p.Leu25Phe (c.73C>T) pathogenic?

EHD2 p.Leu25Phe (c.73C>T) is classified Uncertain significance in EHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: likely pathogenic (0.9512); Absent from gnomAD v4.1.

How common is EHD2 p.Leu25Phe (c.73C>T) in the general population?

EHD2 p.Leu25Phe (c.73C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EHD2 p.Leu25Phe (c.73C>T)?

AlphaMissense predicts likely pathogenic (score 0.9512) — an in-silico prediction, not a clinical call.

EHD2 p.Leu25Phe

c.73C>T · VCV4016975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9512 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9512	likely pathogenic
REVEL	0.356	indeterminate
SaProt	LLR -12.44	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 5.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 25 kb · p 0.00029 · regional, not allelic
Overall
CADD	25.5	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

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: EHD2
Protein: p.Leu25Phe
Coding: c.73C>T
MANE Select: NM_014601
Type: single nucleotide variant
Location: chr19:47716685 (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-leu25phe (accessed [today's date]).

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