Is CDHR1 p.Ala496Pro (c.1486G>C) pathogenic?

CDHR1 p.Ala496Pro (c.1486G>C) is classified Likely pathogenic in CDHR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.9803); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with CDHR1 p.Ala496Pro (c.1486G>C)?

CDHR1 p.Ala496Pro (c.1486G>C) is associated with retinitis pigmentosa (ClinVar).

How common is CDHR1 p.Ala496Pro (c.1486G>C) in the general population?

CDHR1 p.Ala496Pro (c.1486G>C) 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 CDHR1 p.Ala496Pro (c.1486G>C)?

AlphaMissense predicts likely pathogenic (score 0.9803) — an in-silico prediction, not a clinical call.

CDHR1 p.Ala496Pro

c.1486G>C · VCV3544439

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9803 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.9803	likely pathogenic ✓ concordant with ClinVar · top 2% in CDHR1
REVEL	0.779	moderately pathogenic-leaning
SaProt	LLR -13.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4.7, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.035 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: CDHR1
Protein: p.Ala496Pro
Coding: c.1486G>C
MANE Select: NM_033100
Type: single nucleotide variant
Location: chr10:84211648 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 496: the cadherin 5 domain

Full CDHR1 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

CDHR1 p.Tyr509Ter Pathogenic ★★ same condition
CDHR1 p.Gln310Ter Likely pathogenic ★ same condition
CDHR1 p.Ala456Glu Conflicting classifications of pathogenicity ★ ⚠ same condition
CDHR1 p.Ala496_Asp498delinsGly Uncertain significance ★ same residue
CDHR1 p.Gly488Asp Uncertain significance ★ ⚠ same condition
CDHR1 p.Met1Val Conflicting classifications of pathogenicity ★ same condition
CDHR1 p.Pro261= Conflicting classifications of pathogenicity ★ same condition
CDHR1 p.Met1Leu 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/cdhr1-p-ala496pro (accessed [today's date]).

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