Is CDHR2 p.Arg1183Trp (c.3547C>T) pathogenic?

CDHR2 p.Arg1183Trp (c.3547C>T) is classified Uncertain significance in CDHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). AlphaMissense: likely benign (0.2981); Ultra-rare (popmax 0.0164%, mid).

How common is CDHR2 p.Arg1183Trp (c.3547C>T) in the general population?

CDHR2 p.Arg1183Trp (c.3547C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CDHR2 p.Arg1183Trp (c.3547C>T)?

AlphaMissense predicts likely benign (score 0.2981) — an in-silico prediction, not a clinical call.

CDHR2 p.Arg1183Trp

c.3547C>T · VCV3489060

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2981 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2981	likely benign
REVEL	0.612	indeterminate
SaProt	LLR -11.38	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 0.85	GERP 1.4, phastCons 0.24
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.68 · regional, not allelic
Overall
CADD	25.0	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00291% 47/1,612,510 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.0133%	7,492
East Asian	0.0111%	8,978
South Asian	0.00439%	22,756
Remaining individualsnot grpmax-eligible	0.0032%	31,208
European (non-Finnish)	0.00204%	49,123
Finnishnot grpmax-eligible	0.00157%	63,724

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.Arg1183Trp
Coding: c.3547C>T
MANE Select: NM_017675
Type: single nucleotide variant
Location: chr5:176591217 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 2 PDB
Residue 1183: the 'mediates interaction with ush1c and myo7b and is required for proper localization to microvilli tips and function in microvilli organization' region

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

Similar variants

CDHR2 p.Arg1183Gln Uncertain significance ★ ⚠ same residue
CDHR2 p.Arg1183Leu 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-arg1183trp (accessed [today's date]).

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