Is EPHA7 p.Phe182Ser (c.545T>C) pathogenic?

EPHA7 p.Phe182Ser (c.545T>C) is classified Uncertain significance in EPHA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely pathogenic (0.9983); Absent from gnomAD v4.1.

How common is EPHA7 p.Phe182Ser (c.545T>C) in the general population?

EPHA7 p.Phe182Ser (c.545T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPHA7 p.Phe182Ser (c.545T>C)?

AlphaMissense predicts likely pathogenic (score 0.9983) — an in-silico prediction, not a clinical call.

EPHA7 p.Phe182Ser

c.545T>C · VCV3275934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9983 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9983	likely pathogenic · top 5% in EPHA7
REVEL	0.773	moderately pathogenic-leaning
SaProt	LLR -16.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 4,205 bp · p 1.8e-10 · regional, not allelic
Overall
CADD	34.0	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: EPHA7
Protein: p.Phe182Ser
Coding: c.545T>C
MANE Select: NM_004440
Type: single nucleotide variant
Location: chr6:93410788 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.09 · 7 PDB
Residue 182: a β-strand; the eph lbd domain

Full EPHA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHA7 c.2111-2A>G Uncertain significance ★ same type
EPHA7 p.Ala191Ser Uncertain significance ★ ⚠ same type
EPHA7 p.Ala27Glu Uncertain significance ★ ⚠ same type
EPHA7 p.Ala520Asp Uncertain significance ★ ⚠ same type
EPHA7 p.Ala721Ser Uncertain significance ★ ⚠ same type
EPHA7 p.Ala721Val Uncertain significance ★ ⚠ same type
EPHA7 p.Ala761Val Uncertain significance ★ ⚠ same type
EPHA7 p.Ala986Val 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/epha7-p-phe182ser (accessed [today's date]).

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