Is EPHA7 p.Met826Val (c.2476A>G) pathogenic?

EPHA7 p.Met826Val (c.2476A>G) is classified Uncertain significance in EPHA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: ambiguous (0.4865); Very rare (popmax 6.2e-05%).

How common is EPHA7 p.Met826Val (c.2476A>G) in the general population?

EPHA7 p.Met826Val (c.2476A>G) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about EPHA7 p.Met826Val (c.2476A>G)?

AlphaMissense predicts ambiguous (score 0.4865) — an in-silico prediction, not a clinical call.

EPHA7 p.Met826Val

c.2476A>G · VCV4249852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4865 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Computational evidence

Protein change
AlphaMissense	0.4865	ambiguous
REVEL	0.61	indeterminate
SaProt	LLR -12.22	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 115 kb · p 1.6e-06 · regional, not allelic
Overall
CADD	27.1	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

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,816 alleles · very rare exomes 1/1,461,514 · genomes 0/152,302 · joint denominator

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: EPHA7
Protein: p.Met826Val
Coding: c.2476A>G
MANE Select: NM_004440
Type: single nucleotide variant
Location: chr6:93254703 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.09 · 7 PDB
Residue 826: an α-helix; the protein kinase domain

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

Similar variants

EPHA7 p.Met826Thr Uncertain significance ★ ⚠ same residue
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

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-met826val (accessed [today's date]).

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