Is CDHR1 p.Val122Met (c.364G>A) pathogenic?

CDHR1 p.Val122Met (c.364G>A) is classified Uncertain significance in CDHR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-06-09). AlphaMissense: likely benign (0.0817); Ultra-rare (popmax 0.067%, mid); Associated with cone-rod dystrophy 15.

What condition is associated with CDHR1 p.Val122Met (c.364G>A)?

CDHR1 p.Val122Met (c.364G>A) is associated with cone-rod dystrophy 15 (ClinVar).

How common is CDHR1 p.Val122Met (c.364G>A) in the general population?

CDHR1 p.Val122Met (c.364G>A) is ultra-rare (popmax 0.067%, 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.Val122Met (c.364G>A)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

CDHR1 p.Val122Met

c.364G>A · rs886047324 · VCV301214

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.067%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cone-rod dystrophy 15

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.54	GERP -0.14
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.035 · regional, not allelic
Overall
CADD	15.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.067% Middle Eastern · 4/5,968 alleles

Filtering AF 0.0229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00155% 24/1,551,664 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.067%	1,492
East Asian	0.00733%	13,637
Admixed American	0.00392%	25,501
South Asian	0.00357%	28,020
Remaining individualsnot grpmax-eligible	0.00166%	60,118
African / African-American	0.00137%	73,136
European (non-Finnish)	0.000872%	114,700

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.Val122Met
Coding: c.364G>A
MANE Select: NM_033100
dbSNP: rs886047324
Type: single nucleotide variant
Location: chr10:84199047 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 122: the cadherin 1 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-val122met (accessed [today's date]).

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