Is CDHR1 p.Pro261= (c.783G>A) pathogenic?

CDHR1 p.Pro261= (c.783G>A) is classified Conflicting classifications of pathogenicity in CDHR1 (ClinVar, Conflicting submitters, 25 submitters; last evaluated 2026-05-15). Rare (popmax 0.27%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with CDHR1 p.Pro261= (c.783G>A)?

CDHR1 p.Pro261= (c.783G>A) is associated with inherited retinal dystrophy, optic atrophy, retinal disorder (ClinVar).

How common is CDHR1 p.Pro261= (c.783G>A) in the general population?

CDHR1 p.Pro261= (c.783G>A) is rare (popmax 0.27%, nfe) (gnomAD).

CDHR1 p.Pro261=

c.783G>A · rs147346345 · VCV301224

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 25 submitters

gnomAD v4.1

Rare

rare (popmax 0.27%, nfe)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.68	donor loss · deltas
Pangolin	Δ0.55	loss · gain 0.26 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.5	GERP 2.6, phastCons 1
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.27% European (non-Finnish) · 3,191/1,180,036 alleles

Filtering AF 0.263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.259%

Overall 0.237% 3,821/1,614,180 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.564%	177
Ashkenazi Jewishnot grpmax-eligible	0.348%	287
Amishnot grpmax-eligible	0.329%	304
European (non-Finnish)grpmax	0.27%	370
Remaining individualsnot grpmax-eligible	0.187%	534
Admixed American	0.0366%	2,729
African / African-American	0.0187%	5,360
South Asian	0.00988%	10,120
East Asian	0.00223%	44,872

Finnish 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: CDHR1
Protein: p.Pro261=
Coding: c.783G>A
MANE Select: NM_033100
dbSNP: rs147346345
Type: single nucleotide variant
Location: chr10:84203123 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 261: the cadherin 3 domain

Full CDHR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: optic atrophy retinal disorder cone-rod dystrophy 15 retinitis pigmentosa macular dystrophy, retinal, 5 retinitis pigmentosa 65

Similar variants

CDHR1 p.Pro261Leu Uncertain significance ★★ ⚠ same residue
CDHR1 p.Pro261Ser Uncertain significance ★ ⚠ same residue
CDHR1 c.1485+2T>G Pathogenic ★★ same condition
CDHR1 c.525+1G>A Pathogenic ★★ same condition
CDHR1 c.56-1G>A Pathogenic/Likely pathogenic ★★ same condition
CDHR1 c.863-1G>A Pathogenic/Likely pathogenic ★★ same condition
CDHR1 p.Arg407Ter Pathogenic ★★ same condition
CDHR1 p.Tyr509Ter 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-pro261 (accessed [today's date]).

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