Is EPHA10 p.Arg796Pro (c.2387G>C) pathogenic?

EPHA10 p.Arg796Pro (c.2387G>C) is classified Uncertain significance in EPHA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-02). AlphaMissense: likely benign (0.1366); Ultra-rare (popmax 0.0418%, amr).

How common is EPHA10 p.Arg796Pro (c.2387G>C) in the general population?

EPHA10 p.Arg796Pro (c.2387G>C) is ultra-rare (popmax 0.0418%, amr) (gnomAD).

What do computational predictors say about EPHA10 p.Arg796Pro (c.2387G>C)?

AlphaMissense predicts likely benign (score 0.1366) — an in-silico prediction, not a clinical call.

EPHA10 p.Arg796Pro

c.2387G>C · rs372556495 · VCV2403480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1366 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0418%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1366	likely benign
REVEL	0.405	indeterminate
SaProt	LLR -5.31	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 4.8	GERP -0.98, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 47 kb · p 0.69 · regional, not allelic
Overall
CADD	24.1	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 0.0418% Admixed American · 25/59,800 alleles

Filtering AF 0.029% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0248%

Overall 0.00185% 27/1,458,902 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0418%	2,392
European (non-Finnish)	0.00017%	589,682

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: EPHA10
Protein: p.Arg796Pro
Coding: c.2387G>C
MANE Select: NM_001099439
dbSNP: rs372556495
Type: single nucleotide variant
Location: chr1:37720376 (GRCh38)
Gene constraint: LOEUF 1.481 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.56
Residue 796: the protein kinase domain

Full EPHA10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHA10 p.Ala532Thr Benign ★★ same type
EPHA10 p.Pro534= Likely benign ★★ same type
EPHA10 p.Ser574Leu Benign ★★ same type
EPHA10 p.Ala200Ser Uncertain significance ★ ⚠ same type
EPHA10 p.Ala200Val Uncertain significance ★ ⚠ same type
EPHA10 p.Ala213Thr Uncertain significance ★ ⚠ same type
EPHA10 p.Ala323Glu Uncertain significance ★ ⚠ same type
EPHA10 p.Ala388Thr 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/epha10-p-arg796pro (accessed [today's date]).

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