Is EPHA10 p.Arg401Pro (c.1202G>C) pathogenic?

EPHA10 p.Arg401Pro (c.1202G>C) is classified Uncertain significance in EPHA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: likely benign (0.2698); Very rare (popmax 0.00719%, eas).

How common is EPHA10 p.Arg401Pro (c.1202G>C) in the general population?

EPHA10 p.Arg401Pro (c.1202G>C) is very rare (popmax 0.00719%, eas) (gnomAD).

What do computational predictors say about EPHA10 p.Arg401Pro (c.1202G>C)?

AlphaMissense predicts likely benign (score 0.2698) — an in-silico prediction, not a clinical call.

EPHA10 p.Arg401Pro

c.1202G>C · VCV3509254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2698 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00719%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2698	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -11.17	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -2.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 47 kb · p 0.69 · regional, not allelic
Overall
CADD	25.7	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 0.00719% East Asian · 2/27,810 alleles

Filtering AF 0.00119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000445%

Overall 0.00133% 2/150,214 alleles · very rare

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.Arg401Pro
Coding: c.1202G>C
MANE Select: NM_001099439
Type: single nucleotide variant
Location: chr1:37753031 (GRCh38)
Gene constraint: LOEUF 1.481 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.56
Residue 401: the fibronectin type-iii 1 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-arg401pro (accessed [today's date]).

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