Is CDH13 p.Val550Met (c.1648G>A) pathogenic?

CDH13 p.Val550Met (c.1648G>A) is classified Uncertain significance in CDH13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: likely benign (0.0927); Ultra-rare (popmax 0.05%, amr).

How common is CDH13 p.Val550Met (c.1648G>A) in the general population?

CDH13 p.Val550Met (c.1648G>A) is ultra-rare (popmax 0.05%, amr) (gnomAD).

What do computational predictors say about CDH13 p.Val550Met (c.1648G>A)?

AlphaMissense predicts likely benign (score 0.0927) — an in-silico prediction, not a clinical call.

CDH13 p.Val550Met

c.1648G>A · rs548834627 · VCV2602092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0927 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.05%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0927	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -8.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 2, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 1,168 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.05% Admixed American · 30/60,014 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.00799% 129/1,613,566 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.05%	2,000
South Asian	0.045%	2,221
Remaining individualsnot grpmax-eligible	0.00961%	10,410
European (non-Finnish)	0.00441%	22,684

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.Val550Met
Coding: c.1648G>A
MANE Select: NM_001257
dbSNP: rs548834627
Type: single nucleotide variant
Location: chr16:83748217 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.19 · 1 PDB
Residue 550: the cadherin 4 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-val550met (accessed [today's date]).

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