Is CDHR1 p.Arg275Trp (c.823C>T) pathogenic?

CDHR1 p.Arg275Trp (c.823C>T) is classified Uncertain significance in CDHR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-02). AlphaMissense: likely benign (0.0927); Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDHR1 p.Arg275Trp (c.823C>T)?

CDHR1 p.Arg275Trp (c.823C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDHR1 p.Arg275Trp (c.823C>T) in the general population?

CDHR1 p.Arg275Trp (c.823C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about CDHR1 p.Arg275Trp (c.823C>T)?

AlphaMissense predicts likely benign (score 0.0927) — an in-silico prediction, not a clinical call.

CDHR1 p.Arg275Trp

c.823C>T · rs200640039 · VCV862062

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0927 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0927	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP 2.7, phastCons 0.31
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.035 · regional, not allelic
Overall
CADD	24.7	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 0.01% Admixed American · 6/59,986 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00136% 22/1,613,624 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,998
African / African-American	0.00801%	12,479
South Asian	0.00329%	30,355
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000509%	196,619

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.Arg275Trp
Coding: c.823C>T
MANE Select: NM_033100
dbSNP: rs200640039
Type: single nucleotide variant
Location: chr10:84204566 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 275: the cadherin 3 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.Arg275Gln Uncertain significance ★★ ⚠ same residue
CDHR1 p.Arg275= 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

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-arg275trp (accessed [today's date]).

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