Is CDHR1 p.Pro789= (c.2367G>A) pathogenic?

CDHR1 p.Pro789= (c.2367G>A) is classified Conflicting classifications of pathogenicity in CDHR1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0588%, nfe); Associated with cone-rod dystrophy 15.

What condition is associated with CDHR1 p.Pro789= (c.2367G>A)?

CDHR1 p.Pro789= (c.2367G>A) is associated with cone-rod dystrophy 15 (ClinVar).

How common is CDHR1 p.Pro789= (c.2367G>A) in the general population?

CDHR1 p.Pro789= (c.2367G>A) is ultra-rare (popmax 0.0588%, nfe) (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.Pro789=

c.2367G>A · rs150097621 · VCV301258

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0588%, nfe)

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 -4.4	GERP 0.28
Overall
CADD	4.729	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0588% European (non-Finnish) · 694/1,180,024 alleles

Filtering AF 0.0552% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0537%

Overall 0.0476% 768/1,613,590 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0588%	1,700
Admixed American	0.05%	2,000
Remaining individualsnot grpmax-eligible	0.0384%	2,603
Finnishnot grpmax-eligible	0.0204%	4,894
Middle Eastern	0.0164%	6,084
African / African-American	0.00801%	12,485

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.Pro789=
Coding: c.2367G>A
MANE Select: NM_033100
dbSNP: rs150097621
Type: single nucleotide variant
Location: chr10:84214408 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 789: the 'disordered' region

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 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
CDHR1 c.862+4A>C Uncertain significance ★★ same condition
CDHR1 p.Arg407Gln 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-pro789 (accessed [today's date]).

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