Is CDHR2 p.Arg1287Gln (c.3860G>A) pathogenic?

CDHR2 p.Arg1287Gln (c.3860G>A) is classified Likely benign in CDHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: likely benign (0.0856); Ultra-rare (popmax 0.0112%, eas).

How common is CDHR2 p.Arg1287Gln (c.3860G>A) in the general population?

CDHR2 p.Arg1287Gln (c.3860G>A) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about CDHR2 p.Arg1287Gln (c.3860G>A)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

CDHR2 p.Arg1287Gln

c.3860G>A · VCV4651238

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.63	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 2.1	GERP -1, phastCons 0.091
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.68 · regional, not allelic
Overall
CADD	8.479	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 0.0112% East Asian · 5/44,778 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000682% 11/1,612,822 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,956
African / African-American	0.00267%	37,450
European (non-Finnish)	0.000339%	294,840

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.Arg1287Gln
Coding: c.3860G>A
MANE Select: NM_017675
Type: single nucleotide variant
Location: chr5:176595599 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 2 PDB
Residue 1287: the 'mediates interaction with ush1c and myo7b and is required for proper localization to microvilli tips and function in microvilli organization' region; the 'disordered' region

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

Similar variants

CDHR2 p.Arg1287Gly Uncertain significance ★ ⚠ same residue
CDHR2 p.Arg1287Trp Uncertain significance ★ ⚠ same residue
CDHR2 p.Ala1162Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala121Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala13Val Uncertain significance ★ ⚠ same type
CDHR2 p.Ala415Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala423Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala512Thr Uncertain significance ★ ⚠ same type

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-arg1287gln (accessed [today's date]).

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