Is EPHA2 p.Pro47= (c.141G>A) pathogenic?

EPHA2 p.Pro47= (c.141G>A) is classified Likely benign in EPHA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-07). Very rare (popmax 0.00483%, nfe); Associated with cataract 6 multiple types.

What condition is associated with EPHA2 p.Pro47= (c.141G>A)?

EPHA2 p.Pro47= (c.141G>A) is associated with cataract 6 multiple types (ClinVar).

How common is EPHA2 p.Pro47= (c.141G>A) in the general population?

EPHA2 p.Pro47= (c.141G>A) is very rare (popmax 0.00483%, nfe) (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.Pro47=

c.141G>A · rs370213656 · VCV1635413

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

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 -7.3	GERP -4.5
Overall
CADD	7.808	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00483% European (non-Finnish) · 57/1,180,016 alleles

Filtering AF 0.00377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00384% 62/1,613,992 alleles · very rare exomes 57/1,461,816 · genomes 5/152,176 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00483%	20,702
East Asian	0.00445%	22,447
African / African-American	0.00267%	37,458
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Pro47=
Coding: c.141G>A
MANE Select: NM_004431
dbSNP: rs370213656
Type: single nucleotide variant
Location: chr1:16150908 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.73 · 103 PDB
Residue 47: the 'mediates interaction with cldn4' region; the eph lbd domain; 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 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-pro47 (accessed [today's date]).

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