Is EPHA10 p.Ser901Arg (c.2703C>A) pathogenic?

EPHA10 p.Ser901Arg (c.2703C>A) is classified Uncertain significance in EPHA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: ambiguous (0.3486); Very rare (popmax 0.004%, afr).

How common is EPHA10 p.Ser901Arg (c.2703C>A) in the general population?

EPHA10 p.Ser901Arg (c.2703C>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about EPHA10 p.Ser901Arg (c.2703C>A)?

AlphaMissense predicts ambiguous (score 0.3486) — an in-silico prediction, not a clinical call.

EPHA10 p.Ser901Arg

c.2703C>A · VCV4249752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3486 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3486	ambiguous
REVEL	0.209	benign-leaning
SaProt	LLR -7.59	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 47 kb · p 0.69 · regional, not allelic
Overall
CADD	24.2	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 0.004% African / African-American · 3/74,916 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000372% 6/1,613,858 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,972
Admixed American	0.00333%	30,001
East Asian	0.00223%	44,896

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.Ser901Arg
Coding: c.2703C>A
MANE Select: NM_001099439
Type: single nucleotide variant
Location: chr1:37719467 (GRCh38)
Gene constraint: LOEUF 1.481 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.56

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-ser901arg (accessed [today's date]).

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