Is CDHR1 p.Ser357= (c.1071C>T) pathogenic?

CDHR1 p.Ser357= (c.1071C>T) is classified Conflicting classifications of pathogenicity in CDHR1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-05-01). Rare (popmax 0.346%, nfe); Associated with cone-rod dystrophy 15.

What condition is associated with CDHR1 p.Ser357= (c.1071C>T)?

CDHR1 p.Ser357= (c.1071C>T) is associated with cone-rod dystrophy 15 (ClinVar).

How common is CDHR1 p.Ser357= (c.1071C>T) in the general population?

CDHR1 p.Ser357= (c.1071C>T) is rare (popmax 0.346%, 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.Ser357=

c.1071C>T · rs146588811 · VCV301233

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.346%, 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 -2.3	GERP -4.3
Overall
CADD	3.361	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.346% European (non-Finnish) · 4,077/1,180,018 alleles

Filtering AF 0.337% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.333%

Overall 0.269% 4,334/1,614,146 alleles · rare exomes 4,085/1,461,878 · genomes 249/152,268 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.346%	289
Remaining individualsnot grpmax-eligible	0.24%	417
Admixed American	0.0716%	1,396
Finnishnot grpmax-eligible	0.0484%	2,066
African / African-American	0.0386%	2,588
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
East Asian	0.00223%	44,860
South Asian	0.0011%	91,078

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.Ser357=
Coding: c.1071C>T
MANE Select: NM_033100
dbSNP: rs146588811
Type: single nucleotide variant
Location: chr10:84208281 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79

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.Ser357Arg Uncertain significance ★ ⚠ same residue
CDHR1 p.Ser357Asn 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-ser357 (accessed [today's date]).

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