Is CDHR5 p.Arg782Trp (c.2344C>T) pathogenic?

CDHR5 p.Arg782Trp (c.2344C>T) is classified Uncertain significance in CDHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). AlphaMissense: ambiguous (0.4969); Ultra-rare (popmax 0.0483%, sas).

How common is CDHR5 p.Arg782Trp (c.2344C>T) in the general population?

CDHR5 p.Arg782Trp (c.2344C>T) is ultra-rare (popmax 0.0483%, sas) (gnomAD).

What do computational predictors say about CDHR5 p.Arg782Trp (c.2344C>T)?

AlphaMissense predicts ambiguous (score 0.4969) — an in-silico prediction, not a clinical call.

CDHR5 p.Arg782Trp

c.2344C>T · VCV3830284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4969 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, sas)

Computational evidence

Protein change
AlphaMissense	0.4969	ambiguous
REVEL	0.629	indeterminate
SaProt	LLR -10.09	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.54, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 7,548 bp · p 0.00028 · regional, not allelic
Overall
CADD	27.5	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 0.0483% South Asian · 44/91,078 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.0036% 58/1,612,208 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0483%	2,070
Admixed American	0.0117%	8,571
East Asian	0.00446%	22,426
Remaining individualsnot grpmax-eligible	0.0032%	31,224
African / African-American	0.00133%	75,000
European (non-Finnish)	0.00017%	589,783

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: CDHR5
Protein: p.Arg782Trp
Coding: c.2344C>T
MANE Select: NM_021924
Type: single nucleotide variant
Location: chr11:617545 (GRCh38)
Gene constraint: LOEUF 1.479 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.84 · 1 PDB
Residue 782: 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 CDHR5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR5 p.Arg182His Benign ★★ same type
CDHR5 p.Gly298= Benign ★★ same type
CDHR5 p.Ala151Pro Uncertain significance ★ ⚠ same type
CDHR5 p.Ala171Thr Uncertain significance ★ ⚠ same type
CDHR5 p.Ala230Thr Uncertain significance ★ ⚠ same type
CDHR5 p.Ala347Val Uncertain significance ★ ⚠ same type
CDHR5 p.Ala364Val Uncertain significance ★ ⚠ same type
CDHR5 p.Ala369Val 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/cdhr5-p-arg782trp (accessed [today's date]).

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