Is USH2A p.Pro4232Gln (c.12695C>A) pathogenic?

USH2A p.Pro4232Gln (c.12695C>A) is classified Uncertain significance in USH2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2015-01-01). AlphaMissense: ambiguous (0.4227); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with USH2A p.Pro4232Gln (c.12695C>A)?

USH2A p.Pro4232Gln (c.12695C>A) is associated with retinitis pigmentosa (ClinVar).

How common is USH2A p.Pro4232Gln (c.12695C>A) in the general population?

USH2A p.Pro4232Gln (c.12695C>A) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about USH2A p.Pro4232Gln (c.12695C>A)?

AlphaMissense predicts ambiguous (score 0.4227) — an in-silico prediction, not a clinical call.

USH2A p.Pro4232Gln

c.12695C>A · rs745371873 · VCV438007

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4227 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.4227	ambiguous
REVEL	0.671	pathogenic-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 797 kb · p 0.00011 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: USH2A
Protein: p.Pro4232Gln
Coding: c.12695C>A
MANE Select: NM_206933
dbSNP: rs745371873
Type: single nucleotide variant
Location: chr1:215675216 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 4232: a UniProt-annotated variant site (in ush2a); the fibronectin type-iii 27 domain

Full USH2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

USH2A p.Pro4232= Benign/Likely benign ★★ same residue
USH2A p.Pro4232Leu Pathogenic ★ ⚠ same residue
USH2A p.Pro4232Thr Likely pathogenic ★ ⚠ same residue
USH2A c.12295-3T>A Pathogenic ★★★ same condition
USH2A c.8559-2A>G Pathogenic ★★★ same condition
USH2A c.8682-9A>G Pathogenic ★★★ same condition
USH2A p.Ala4740Asp Pathogenic ★★★ ⚠ same condition
USH2A p.Arg3905Cys Pathogenic ★★★ ⚠ 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/ush2a-p-pro4232gln (accessed [today's date]).

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