Is CDHR1 p.Ser490= (c.1470C>T) pathogenic?

CDHR1 p.Ser490= (c.1470C>T) is classified Conflicting classifications of pathogenicity in CDHR1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-10). Ultra-rare (popmax 0.0704%, nfe); Associated with cone-rod dystrophy 15.

What condition is associated with CDHR1 p.Ser490= (c.1470C>T)?

CDHR1 p.Ser490= (c.1470C>T) is associated with cone-rod dystrophy 15 (ClinVar).

How common is CDHR1 p.Ser490= (c.1470C>T) in the general population?

CDHR1 p.Ser490= (c.1470C>T) is ultra-rare (popmax 0.0704%, 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.Ser490=

c.1470C>T · rs150577739 · VCV301242

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 0.0704%, 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 -13	GERP -4.5
Overall
CADD	0.477	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0704% European (non-Finnish) · 831/1,180,040 alleles

Filtering AF 0.0664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0648%

Overall 0.0571% 921/1,614,100 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0704%	1,420
Remaining individualsnot grpmax-eligible	0.0624%	1,602
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,742
Admixed American	0.0267%	3,751
Middle Eastern	0.0164%	6,082
African / African-American	0.016%	6,245
South Asian	0.00439%	22,773
Finnishnot grpmax-eligible	0.00156%	64,032

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.Ser490=
Coding: c.1470C>T
MANE Select: NM_033100
dbSNP: rs150577739
Type: single nucleotide variant
Location: chr10:84211150 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 490: 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 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-ser490 (accessed [today's date]).

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