Is EPHA7 p.Ile783Val (c.2347A>G) pathogenic?

EPHA7 p.Ile783Val (c.2347A>G) is classified Uncertain significance in EPHA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-21). AlphaMissense: likely benign (0.1427); Ultra-rare (popmax 0.0253%, sas).

How common is EPHA7 p.Ile783Val (c.2347A>G) in the general population?

EPHA7 p.Ile783Val (c.2347A>G) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about EPHA7 p.Ile783Val (c.2347A>G)?

AlphaMissense predicts likely benign (score 0.1427) — an in-silico prediction, not a clinical call.

EPHA7 p.Ile783Val

c.2347A>G · VCV4664754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1427 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1427	likely benign
REVEL	0.445	indeterminate
SaProt	LLR -8.06	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 4.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 115 kb · p 1.6e-06 · regional, not allelic
Overall
CADD	23.1	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

Grpmax group 0.0253% South Asian · 23/91,086 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00167% 27/1,613,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
African / African-American	0.00133%	74,926
European (non-Finnish)	0.000169%	589,998

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.Ile783Val
Coding: c.2347A>G
MANE Select: NM_004440
Type: single nucleotide variant
Location: chr6:93255863 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.09 · 7 PDB
Residue 783: the protein kinase 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-ile783val (accessed [today's date]).

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