Is EPHA2 p.Pro786= (c.2358G>A) pathogenic?

EPHA2 p.Pro786= (c.2358G>A) is classified Likely benign in EPHA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-03). Very rare (popmax 0.00329%, sas); Associated with cataract 6 multiple types.

What condition is associated with EPHA2 p.Pro786= (c.2358G>A)?

EPHA2 p.Pro786= (c.2358G>A) is associated with cataract 6 multiple types (ClinVar).

How common is EPHA2 p.Pro786= (c.2358G>A) in the general population?

EPHA2 p.Pro786= (c.2358G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Early onset non-syndromic cataract inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EPHA2 p.Pro786=

c.2358G>A · VCV4737096

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

cataract 6 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -4.5
Overall
CADD	0.111	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,086 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00155% 25/1,613,878 alleles · very rare exomes 21/1,461,702 · genomes 4/152,176 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,362
European (non-Finnish)	0.00169%	59,001
Finnishnot grpmax-eligible	0.00156%	63,898
African / African-American	0.00133%	74,926

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: EPHA2
Protein: p.Pro786=
Coding: c.2358G>A
MANE Select: NM_004431
Type: single nucleotide variant
Location: chr1:16131838 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.73 · 103 PDB
Residue 786: the 'mediates interaction with arhgef16 and elmo2' region; an α-helix; the protein kinase domain

Full EPHA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 6 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

EPHA2 c.2826-9G>A Pathogenic ★★ same condition
EPHA2 p.Ala321Val Uncertain significance ★★ ⚠ same condition
EPHA2 p.Arg175His Uncertain significance ★★ ⚠ same condition
EPHA2 p.Arg195Cys Uncertain significance ★★ ⚠ same condition
EPHA2 p.Arg315Trp Uncertain significance ★★ ⚠ same condition
EPHA2 p.Arg428His Uncertain significance ★★ ⚠ same condition
EPHA2 p.Arg560His Uncertain significance ★★ ⚠ same condition
EPHA2 p.Arg566His Uncertain significance ★★ ⚠ same condition

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/epha2-p-pro786 (accessed [today's date]).

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