Is CDHR1 p.Cys650Arg (c.1948T>C) pathogenic?

CDHR1 p.Cys650Arg (c.1948T>C) is classified Uncertain significance in CDHR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-11). AlphaMissense: likely benign (0.1107); Ultra-rare (popmax 0.02%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDHR1 p.Cys650Arg (c.1948T>C)?

CDHR1 p.Cys650Arg (c.1948T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDHR1 p.Cys650Arg (c.1948T>C) in the general population?

CDHR1 p.Cys650Arg (c.1948T>C) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about CDHR1 p.Cys650Arg (c.1948T>C)?

AlphaMissense predicts likely benign (score 0.1107) — an in-silico prediction, not a clinical call.

CDHR1 p.Cys650Arg

c.1948T>C · rs555641256 · VCV1491435

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1107	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -2.93	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 -0.39	GERP -3.7
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.035 · regional, not allelic
Overall
CADD	15.68	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 0.02% Admixed American · 12/60,028 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00155% 25/1,614,230 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,002
Remaining individualsnot grpmax-eligible	0.0048%	20,836
African / African-American	0.00266%	37,535
European (non-Finnish)	0.000678%	147,501

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.Cys650Arg
Coding: c.1948T>C
MANE Select: NM_033100
dbSNP: rs555641256
Type: single nucleotide variant
Location: chr10:84213256 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 650: the cadherin 6 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

Similar variants

CDHR1 p.Cys650= Likely benign ★★ same residue
CDHR1 p.Ala106Thr Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala10Val Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala118Asp Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala132Val Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala292Asp Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala393Gly Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala493Val 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-cys650arg (accessed [today's date]).

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