Is CDH23 p.Arg2613Cys (c.7837C>T) pathogenic?

CDH23 p.Arg2613Cys (c.7837C>T) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-08). AlphaMissense: ambiguous (0.5146); Very rare (popmax 0.00808%, afr).

How common is CDH23 p.Arg2613Cys (c.7837C>T) in the general population?

CDH23 p.Arg2613Cys (c.7837C>T) is very rare (popmax 0.00808%, afr) (gnomAD).

What do computational predictors say about CDH23 p.Arg2613Cys (c.7837C>T)?

AlphaMissense predicts ambiguous (score 0.5146) — an in-silico prediction, not a clinical call.

CDH23 p.Arg2613Cys

c.7837C>T · rs759531384 · VCV1431163

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00808%, afr)

Computational evidence

Protein change
AlphaMissense	0.5146	ambiguous
REVEL	0.486	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 12 kb · p 0.86 · regional, not allelic
Overall
CADD	26.9	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 0.00808% African / African-American · 6/74,252 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0024%

Overall 0.000938% 15/1,598,536 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00808%	12,375
Remaining individualsnot grpmax-eligible	0.00323%	30,963
European (non-Finnish)	0.000597%	167,613

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: CDH23
Protein: p.Arg2613Cys
Coding: c.7837C>T
MANE Select: NM_022124
dbSNP: rs759531384
Type: single nucleotide variant
Location: chr10:71803385 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

Full CDH23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH23 p.Arg2613His Uncertain significance same residue
CDH23 p.Arg2029Trp Pathogenic ★★★ ⚠ same type
CDH23 p.Asp127Gly Likely pathogenic ★★★ same type
CDH23 p.Glu956Lys Pathogenic ★★★ same type
CDH23 p.Pro240Leu Pathogenic ★★★ same type
CDH23 c.1515-12G>A Uncertain significance ★★★ same type
CDH23 p.Ala3190Val Uncertain significance ★★★ ⚠ same type
CDH23 p.Arg301Gln 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/cdh23-p-arg2613cys (accessed [today's date]).

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