Is CDHR2 p.Arg285Trp (c.853C>T) pathogenic?

CDHR2 p.Arg285Trp (c.853C>T) is classified Uncertain significance in CDHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-28). AlphaMissense: likely benign (0.146); Very rare (popmax 0.00706%, eas).

How common is CDHR2 p.Arg285Trp (c.853C>T) in the general population?

CDHR2 p.Arg285Trp (c.853C>T) is very rare (popmax 0.00706%, eas) (gnomAD).

What do computational predictors say about CDHR2 p.Arg285Trp (c.853C>T)?

AlphaMissense predicts likely benign (score 0.146) — an in-silico prediction, not a clinical call.

CDHR2 p.Arg285Trp

c.853C>T · VCV4832167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00706%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.146	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -10.19	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -1.8, phastCons 0.41
Regional constraint	o/e 0.93	unconstrained · MANE · 19 kb · p 0.025 · regional, not allelic
Overall
CADD	14.43	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 0.00706% East Asian · 3/42,470 alleles

Filtering AF 0.00187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00102%

Overall 0.00101% 16/1,576,538 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00706%	14,157
African / African-American	0.00271%	36,923
South Asian	0.00229%	43,680
European (non-Finnish)	0.000775%	128,966

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: CDHR2
Protein: p.Arg285Trp
Coding: c.853C>T
MANE Select: NM_017675
Type: single nucleotide variant
Location: chr5:176575732 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 2 PDB
Residue 285: the cadherin 3 domain

Full CDHR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/cdhr2-p-arg285trp (accessed [today's date]).

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