Is EPHA2 p.Pro238= (c.714G>C) pathogenic?

EPHA2 p.Pro238= (c.714G>C) is classified Benign in EPHA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-10-19). Rare (popmax 0.989%, sas); Associated with cataract 6 multiple types.

What condition is associated with EPHA2 p.Pro238= (c.714G>C)?

EPHA2 p.Pro238= (c.714G>C) is associated with cataract 6 multiple types (ClinVar).

How common is EPHA2 p.Pro238= (c.714G>C) in the general population?

EPHA2 p.Pro238= (c.714G>C) is rare (popmax 0.989%, 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.Pro238=

c.714G>C · rs36037949 · VCV293441

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.989%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.2
Overall
CADD	0.007	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.989% South Asian · 901/91,090 alleles

Filtering AF 0.936% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.914%

Overall 0.0832% 1,342/1,613,852 alleles · rare exomes 1,259/1,461,468 · genomes 83/152,384 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.989%	101
Middle Eastern	0.544%	184
Remaining individualsnot grpmax-eligible	0.117%	856
Admixed American	0.0866%	1,154
European (non-Finnish)	0.0236%	4,229
African / African-American	0.00533%	18,770

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.Pro238=
Coding: c.714G>C
MANE Select: NM_004431
dbSNP: rs36037949
Type: single nucleotide variant
Location: chr1:16148487 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.73 · 103 PDB
Residue 238: a β-strand

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 p.Pro238Ala Uncertain significance ★ ⚠ same residue
EPHA2 p.Pro238Leu Uncertain significance ★ ⚠ same residue
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

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-pro238 (accessed [today's date]).

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