Is EPHA2 p.Arg792= (c.2374C>A) pathogenic?

EPHA2 p.Arg792= (c.2374C>A) is classified Benign/Likely benign in EPHA2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-11-13). Rare (popmax 0.686%, afr); Associated with cataract 6 multiple types.

What condition is associated with EPHA2 p.Arg792= (c.2374C>A)?

EPHA2 p.Arg792= (c.2374C>A) is associated with cataract 6 multiple types (ClinVar).

How common is EPHA2 p.Arg792= (c.2374C>A) in the general population?

EPHA2 p.Arg792= (c.2374C>A) is rare (popmax 0.686%, afr) (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.Arg792=

c.2374C>A · rs55869078 · VCV293411

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.686%, afr)

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 12	GERP 2.2, phastCons 1
Overall
CADD	14.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.686% African / African-American · 515/75,030 alleles

Filtering AF 0.637% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.618%

Overall 0.0811% 1,309/1,614,062 alleles · rare exomes 958/1,461,770 · genomes 351/152,292 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.79%	56
African / African-Americangrpmax	0.686%	146
Remaining individualsnot grpmax-eligible	0.186%	539
Admixed American	0.0616%	1,622
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00915%	10,926
South Asian	0.0011%	91,088

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg792=
Coding: c.2374C>A
MANE Select: NM_004431
dbSNP: rs55869078
Type: single nucleotide variant
Location: chr1:16131822 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.73 · 103 PDB
Residue 792: the 'mediates interaction with arhgef16 and elmo2' region; 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 p.Arg792Trp 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
EPHA2 p.Arg560His 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-arg792 (accessed [today's date]).

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