Is CDH15 p.Pro150Ser (c.448C>T) pathogenic?

CDH15 p.Pro150Ser (c.448C>T) is classified Uncertain significance in CDH15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.9943); Absent from gnomAD v4.1.

How common is CDH15 p.Pro150Ser (c.448C>T) in the general population?

CDH15 p.Pro150Ser (c.448C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH15 p.Pro150Ser (c.448C>T)?

AlphaMissense predicts likely pathogenic (score 0.9943) — an in-silico prediction, not a clinical call.

CDH15 p.Pro150Ser

c.448C>T · VCV4835453

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9943 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9943	likely pathogenic · top 1% in CDH15
REVEL	0.934	strongly pathogenic-leaning
SaProt	LLR -15.18	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 23 kb · p 5e-10 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: CDH15
Protein: p.Pro150Ser
Coding: c.448C>T
MANE Select: NM_004933
Type: single nucleotide variant
Location: chr16:89183638 (GRCh38)
Gene constraint: LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 150: the cadherin 1 domain

Full CDH15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH3 p.Ala150Thr Uncertain significance ★★ ⚠ same residue
CDH3 c.1796-2A>G Pathogenic ★★ same type
CDH3 c.691+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH3 p.Arg103Ter Pathogenic ★★ same type
CDH3 p.Arg221Ter Pathogenic ★★ same type
CDH3 p.Arg503His Pathogenic/Likely pathogenic ★★ ⚠ same type
CDH3 p.Gln299Ter Pathogenic ★★ same type
CDH3 p.Glu708Ter Likely pathogenic ★★ 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/cdh15-p-pro150ser (accessed [today's date]).

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