Is EPHA10 p.Pro27Arg (c.80C>G) pathogenic?

EPHA10 p.Pro27Arg (c.80C>G) is classified Uncertain significance in EPHA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.0833); Rare (popmax 0.132%, mid).

How common is EPHA10 p.Pro27Arg (c.80C>G) in the general population?

EPHA10 p.Pro27Arg (c.80C>G) is rare (popmax 0.132%, mid) (gnomAD).

What do computational predictors say about EPHA10 p.Pro27Arg (c.80C>G)?

AlphaMissense predicts likely benign (score 0.0833) — an in-silico prediction, not a clinical call.

EPHA10 p.Pro27Arg

c.80C>G · rs768050906 · VCV2325083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0833 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0833	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -8.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP -0.45, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 47 kb · p 0.69 · regional, not allelic
Overall
CADD	19.29	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 0.132% Middle Eastern · 8/6,078 alleles

Filtering AF 0.0655% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0477%

Overall 0.00397% 64/1,610,324 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	760
Admixed American	0.00839%	11,922
European (non-Finnish)	0.00416%	24,064
African / African-American	0.00267%	37,441

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.Pro27Arg
Coding: c.80C>G
MANE Select: NM_001099439
dbSNP: rs768050906
Type: single nucleotide variant
Location: chr1:37764987 (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.Pro27Leu Uncertain significance ★ ⚠ same residue
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

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-pro27arg (accessed [today's date]).

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