Is EPHA2 p.Trp14Ter (c.41G>A) pathogenic?

EPHA2 p.Trp14Ter (c.41G>A) is classified Pathogenic in EPHA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-03). No allele count reported in gnomAD v4.1 (AN 1,487,910); Associated with aniridia.

What condition is associated with EPHA2 p.Trp14Ter (c.41G>A)?

EPHA2 p.Trp14Ter (c.41G>A) is associated with aniridia, cataract (ClinVar).

How common is EPHA2 p.Trp14Ter (c.41G>A) in the general population?

EPHA2 p.Trp14Ter (c.41G>A) is no allele count reported in gnomAD v4.1 (AN 1,487,910) (gnomAD).

EPHA2 p.Trp14Ter

c.41G>A · rs2124283411 · VCV1341682

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,487,910)

Conditions

aniridia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.61, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,487,910). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EPHA2
Protein: p.Trp14Ter
Coding: c.41G>A
MANE Select: NM_004431
dbSNP: rs2124283411
Type: single nucleotide variant
Location: chr1:16155892 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.73 · 103 PDB
Residue 14: the 'mediates interaction with cldn4' region

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

Disease context

aniridia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cataract

Similar variants

EPHA2 p.Trp14Gly Uncertain significance ★ ⚠ same residue
EPHA2 c.2826-9G>A Pathogenic ★★ same type
EPHA2 p.Ala321Val Uncertain significance ★★ ⚠ same type
EPHA2 p.Arg175His Uncertain significance ★★ ⚠ same type
EPHA2 p.Arg195Cys Uncertain significance ★★ ⚠ same type
EPHA2 p.Arg315Trp Uncertain significance ★★ ⚠ same type
EPHA2 p.Arg428His Uncertain significance ★★ ⚠ same type
EPHA2 p.Arg560His 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/epha2-p-trp14ter (accessed [today's date]).

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