Is CDHR1 p.Val210Met (c.628G>A) pathogenic?

CDHR1 p.Val210Met (c.628G>A) is classified Uncertain significance in CDHR1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.2004); Ultra-rare (popmax 0.0987%, mid); Associated with Inborn genetic diseases.

What condition is associated with CDHR1 p.Val210Met (c.628G>A)?

CDHR1 p.Val210Met (c.628G>A) is associated with Inborn genetic diseases, cone-rod dystrophy 15, inherited retinal dystrophy (ClinVar).

How common is CDHR1 p.Val210Met (c.628G>A) in the general population?

CDHR1 p.Val210Met (c.628G>A) is ultra-rare (popmax 0.0987%, mid) (gnomAD).

What do computational predictors say about CDHR1 p.Val210Met (c.628G>A)?

AlphaMissense predicts likely benign (score 0.2004) — an in-silico prediction, not a clinical call.

CDHR1 p.Val210Met

c.628G>A · rs774747506 · VCV444229

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2004 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0987%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2004	likely benign
REVEL	0.379	indeterminate
SaProt	LLR -10.83	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 3.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.035 · regional, not allelic
Overall
CADD	25.4	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 0.0987% Middle Eastern · 6/6,082 alleles

Filtering AF 0.0429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.0033% 53/1,604,612 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0987%	1,014
Remaining individualsnot grpmax-eligible	0.00801%	12,482
South Asian	0.00659%	15,173
European (non-Finnish)	0.00288%	34,689
East Asian	0.00223%	44,874
African / African-American	0.00133%	74,914

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.Val210Met
Coding: c.628G>A
MANE Select: NM_033100
dbSNP: rs774747506
Type: single nucleotide variant
Location: chr10:84201909 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 210: the cadherin 2 domain

Full CDHR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cone-rod dystrophy 15 inherited retinal dystrophy

Similar variants

CDHR1 p.Val210= Likely benign ★ 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-val210met (accessed [today's date]).

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