Is EPHA5 p.Ala38Pro (c.112G>C) pathogenic?

EPHA5 p.Ala38Pro (c.112G>C) is classified Uncertain significance in EPHA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: likely benign (0.0785); Absent from gnomAD v4.1.

How common is EPHA5 p.Ala38Pro (c.112G>C) in the general population?

EPHA5 p.Ala38Pro (c.112G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPHA5 p.Ala38Pro (c.112G>C)?

AlphaMissense predicts likely benign (score 0.0785) — an in-silico prediction, not a clinical call.

EPHA5 p.Ala38Pro

c.112G>C · VCV3275922

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0785 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0785	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -6.08	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 0.96	GERP 0.82, phastCons 0.65
Regional constraint	o/e 1.02	unconstrained · MANE · 68 kb · p 0.72 · regional, not allelic
Overall
CADD	19.67	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPHA5
Protein: p.Ala38Pro
Coding: c.112G>C
MANE Select: NM_001281766
Type: single nucleotide variant
Location: chr4:65669631 (GRCh38)
Gene constraint: LOEUF 0.711 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.10 · 2 PDB

Full EPHA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHA5 c.2173+8T>A Benign ★★ same type
EPHA5 p.Ala646= Benign ★★ same type
EPHA5 p.Glu528Gln Benign ★★ ⚠ same type
EPHA5 p.Ser652Thr Likely benign ★★ ⚠ same type
EPHA5 c.1794-9583G>A Uncertain significance ★ ⚠ same type
EPHA5 c.1794-9635T>G Uncertain significance ★ ⚠ same type
EPHA5 p.Ala123Val Uncertain significance ★ ⚠ same type
EPHA5 p.Ala332Gly 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/epha5-p-ala38pro (accessed [today's date]).

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