Is CDHR1 p.Pro350= (c.1050G>A) pathogenic?

CDHR1 p.Pro350= (c.1050G>A) is classified Conflicting classifications of pathogenicity in CDHR1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.0245%, eas); Associated with cone-rod dystrophy 15.

What condition is associated with CDHR1 p.Pro350= (c.1050G>A)?

CDHR1 p.Pro350= (c.1050G>A) is associated with cone-rod dystrophy 15 (ClinVar).

How common is CDHR1 p.Pro350= (c.1050G>A) in the general population?

CDHR1 p.Pro350= (c.1050G>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

How is Cone rod dystrophy inherited?

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

CDHR1 p.Pro350=

c.1050G>A · rs199721776 · VCV301232

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Conditions

cone-rod dystrophy 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.6	GERP -9.1
Overall
CADD	0.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,880 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00254% 41/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,080
African / African-American	0.00534%	18,724
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.00186%	53,637
Admixed American	0.00167%	59,988
South Asian	0.0011%	91,080

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.Pro350=
Coding: c.1050G>A
MANE Select: NM_033100
dbSNP: rs199721776
Type: single nucleotide variant
Location: chr10:84208260 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 350: the cadherin 3 domain

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

Disease context

cone-rod dystrophy 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CDHR1 p.Pro350Leu Uncertain significance ★★ ⚠ same residue
CDHR1 p.Pro350Ser 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 c.1554-3C>A 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/cdhr1-p-pro350 (accessed [today's date]).

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