Is CDH23 p.Phe3083Ser (c.9248T>C) pathogenic?

CDH23 p.Phe3083Ser (c.9248T>C) is classified Uncertain significance in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely pathogenic (0.6268); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDH23 p.Phe3083Ser (c.9248T>C)?

CDH23 p.Phe3083Ser (c.9248T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDH23 p.Phe3083Ser (c.9248T>C) in the general population?

CDH23 p.Phe3083Ser (c.9248T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH23 p.Phe3083Ser (c.9248T>C)?

AlphaMissense predicts likely pathogenic (score 0.6268) — an in-silico prediction, not a clinical call.

CDH23 p.Phe3083Ser

c.9248T>C · rs2494453025 · VCV2554043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6268 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6268	likely pathogenic
REVEL	0.351	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 12 kb · p 0.86 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDH23
Protein: p.Phe3083Ser
Coding: c.9248T>C
MANE Select: NM_022124
dbSNP: rs2494453025
Type: single nucleotide variant
Location: chr10:71811560 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH23 p.Phe3083Ile Uncertain significance ★★ same residue
CDH23 p.Phe3083fs Pathogenic/Likely pathogenic ★★ same residue
CDH23 p.Ala129Thr Uncertain significance ★★ ⚠ same condition
CDH23 p.Ala1464Glu Uncertain significance ★★ ⚠ same condition
CDH23 p.Ala1482Val Uncertain significance ★★ ⚠ same condition
CDH23 p.Ala1673Val Uncertain significance ★★ same condition
CDH23 p.Ala1878Thr Uncertain significance ★★ same condition
CDH23 p.Ala1974Thr Uncertain significance ★★ ⚠ same condition

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-phe3083ser (accessed [today's date]).

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