Is CDHR1 p.Val183Met (c.547G>A) pathogenic?

CDHR1 p.Val183Met (c.547G>A) is classified Conflicting classifications of pathogenicity in CDHR1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.067); Rare (popmax 0.429%, mid); Associated with cone-rod dystrophy 15.

What condition is associated with CDHR1 p.Val183Met (c.547G>A)?

CDHR1 p.Val183Met (c.547G>A) is associated with cone-rod dystrophy 15 (ClinVar).

How common is CDHR1 p.Val183Met (c.547G>A) in the general population?

CDHR1 p.Val183Met (c.547G>A) is rare (popmax 0.429%, mid) (gnomAD).

How is Cone rod dystrophy inherited?

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

What do computational predictors say about CDHR1 p.Val183Met (c.547G>A)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

CDHR1 p.Val183Met

c.547G>A · rs142109115 · VCV301219

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.429%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cone-rod dystrophy 15

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.3	GERP -9.5
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.035 · regional, not allelic
Overall
CADD	0.055	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.429% Middle Eastern · 26/6,062 alleles

Filtering AF 0.301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.258%

Overall 0.0305% 491/1,610,444 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.429%	233
African / African-American	0.193%	518
Admixed American	0.11%	909
Remaining individualsnot grpmax-eligible	0.0528%	1,894
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,700
European (non-Finnish)	0.0174%	5,756
South Asian	0.00769%	13,011
East Asian	0.00223%	44,878

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.Val183Met
Coding: c.547G>A
MANE Select: NM_033100
dbSNP: rs142109115
Type: single nucleotide variant
Location: chr10:84201828 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 183: the cadherin 2 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-val183met (accessed [today's date]).

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