Is CDH23 p.Pro2707Leu (c.8120C>T) pathogenic?

CDH23 p.Pro2707Leu (c.8120C>T) is classified Benign/Likely benign in CDH23 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.1477); Rare (popmax 0.924%, sas).

How common is CDH23 p.Pro2707Leu (c.8120C>T) in the general population?

CDH23 p.Pro2707Leu (c.8120C>T) is rare (popmax 0.924%, sas) (gnomAD).

What do computational predictors say about CDH23 p.Pro2707Leu (c.8120C>T)?

AlphaMissense predicts likely benign (score 0.1477) — an in-silico prediction, not a clinical call.

CDH23 p.Pro2707Leu

c.8120C>T · rs373230009 · VCV735476

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1477 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.924%, sas)

Computational evidence

Protein change
AlphaMissense	0.1477	likely benign
REVEL	0.335	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 12 kb · p 0.86 · regional, not allelic
Overall
CADD	28.0	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 0.924% South Asian · 796/86,186 alleles

Filtering AF 0.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.849%

Overall 0.0615% 971/1,579,510 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.924%	108
Middle Eastern	0.415%	241
Remaining individualsnot grpmax-eligible	0.0931%	1,074
Admixed American	0.0254%	3,935
East Asian	0.00698%	14,330
European (non-Finnish)	0.00645%	15,503
African / African-American	0.00135%	74,324

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.Pro2707Leu
Coding: c.8120C>T
MANE Select: NM_022124
dbSNP: rs373230009
Type: single nucleotide variant
Location: chr10:71806223 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2707: the cadherin 25 domain

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

Similar variants

CDH23 p.Pro2707= Benign/Likely benign ★★ same residue
CDH23 p.Pro2707Ser 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

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-pro2707leu (accessed [today's date]).

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