Is CDHR1 p.Gly487= (c.1461G>A) pathogenic?

CDHR1 p.Gly487= (c.1461G>A) is classified Conflicting classifications of pathogenicity in CDHR1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-24). Rare (popmax 0.253%, nfe); Associated with cone-rod dystrophy 15.

What condition is associated with CDHR1 p.Gly487= (c.1461G>A)?

CDHR1 p.Gly487= (c.1461G>A) is associated with cone-rod dystrophy 15 (ClinVar).

How common is CDHR1 p.Gly487= (c.1461G>A) in the general population?

CDHR1 p.Gly487= (c.1461G>A) is rare (popmax 0.253%, 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.Gly487=

c.1461G>A · rs141787212 · VCV301240

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.253%, 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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.98 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.26	GERP 1.7, phastCons 0.94
Overall
CADD	7.124	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.253% European (non-Finnish) · 2,989/1,180,040 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.243%

Overall 0.209% 3,369/1,614,234 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.253%	395
Admixed American	0.163%	613
South Asian	0.157%	637
Remaining individualsnot grpmax-eligible	0.12%	833
Middle Eastern	0.066%	1,516
Finnishnot grpmax-eligible	0.0531%	1,883
African / African-American	0.0346%	2,887

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.Gly487=
Coding: c.1461G>A
MANE Select: NM_033100
dbSNP: rs141787212
Type: single nucleotide variant
Location: chr10:84211141 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 487: the cadherin 5 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.Gly487Glu 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
CDHR1 c.862+4A>C 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-gly487 (accessed [today's date]).

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