Is EHD4 p.Ile513Phe (c.1537A>T) pathogenic?

EHD4 p.Ile513Phe (c.1537A>T) is classified Uncertain significance in EHD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely pathogenic (0.5881); Absent from gnomAD v4.1.

How common is EHD4 p.Ile513Phe (c.1537A>T) in the general population?

EHD4 p.Ile513Phe (c.1537A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EHD4 p.Ile513Phe (c.1537A>T)?

AlphaMissense predicts likely pathogenic (score 0.5881) — an in-silico prediction, not a clinical call.

EHD4 p.Ile513Phe

c.1537A>T · VCV4247555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5881 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5881	likely pathogenic
REVEL	0.158	moderately benign-leaning
SaProt	LLR -10.60	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 72 kb · p 0.00019 · regional, not allelic
Overall
CADD	24.8	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

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: EHD4
Protein: p.Ile513Phe
Coding: c.1537A>T
MANE Select: NM_139265
Type: single nucleotide variant
Location: chr15:41900734 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.19
Residue 513: the eh domain; the ef-hand domain

Full EHD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EHD4 p.Ala194Gly Uncertain significance ★ ⚠ same type
EHD4 p.Ala276Thr Uncertain significance ★ ⚠ same type
EHD4 p.Ala304Val Uncertain significance ★ ⚠ same type
EHD4 p.Ala437Thr Uncertain significance ★ ⚠ same type
EHD4 p.Ala505Pro Uncertain significance ★ ⚠ same type
EHD4 p.Ala9Glu Uncertain significance ★ ⚠ same type
EHD4 p.Arg14Ser Uncertain significance ★ ⚠ same type
EHD4 p.Arg211Trp 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/ehd4-p-ile513phe (accessed [today's date]).

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