Is CDH13 p.Pro154Ser (c.460C>T) pathogenic?

CDH13 p.Pro154Ser (c.460C>T) is classified Uncertain significance in CDH13 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-08). AlphaMissense: ambiguous (0.4904); Very rare (popmax 0.00167%, amr).

How common is CDH13 p.Pro154Ser (c.460C>T) in the general population?

CDH13 p.Pro154Ser (c.460C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CDH13 p.Pro154Ser (c.460C>T)?

AlphaMissense predicts ambiguous (score 0.4904) — an in-silico prediction, not a clinical call.

CDH13 p.Pro154Ser

c.460C>T · rs1164736342 · VCV2263009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4904 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4904	ambiguous
REVEL	0.227	benign-leaning
SaProt	LLR -9.96	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 1,168 kb · p 1.2e-06 · 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 0.00167% Admixed American · 1/59,972 alleles

Overall 6.89e-05% 1/1,451,090 alleles · very rare

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: CDH13
Protein: p.Pro154Ser
Coding: c.460C>T
MANE Select: NM_001257
dbSNP: rs1164736342
Type: single nucleotide variant
Location: chr16:83125478 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.19 · 1 PDB
Residue 154: the cadherin 1 domain

Full CDH13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH13 c.1102-6T>C Benign ★★ same type
CDH13 c.1284+90A>G Benign ★★ same type
CDH13 c.1539-109T>C Benign ★★ same type
CDH13 c.1681+64T>C Benign ★★ same type
CDH13 c.1682-151C>T Benign ★★ same type
CDH13 c.1682-180G>A Benign ★★ same type
CDH13 c.1682-59A>G Benign ★★ same type
CDH13 c.1682-62G>A Benign ★★ 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/cdh13-p-pro154ser (accessed [today's date]).

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