Is CDH15 p.Asp663= (c.1989C>T) pathogenic?

CDH15 p.Asp663= (c.1989C>T) is classified Likely benign in CDH15 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-23). Ultra-rare (popmax 0.0166%, mid); Associated with CDH15-related disorder.

What condition is associated with CDH15 p.Asp663= (c.1989C>T)?

CDH15 p.Asp663= (c.1989C>T) is associated with CDH15-related disorder (ClinVar).

How common is CDH15 p.Asp663= (c.1989C>T) in the general population?

CDH15 p.Asp663= (c.1989C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

CDH15 p.Asp663=

c.1989C>T · rs769804850 · VCV3039040

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Conditions

CDH15-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.42, phastCons 1
Overall
CADD	10.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,014 alleles

Filtering AF 0.000504% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000368%

Overall 0.000831% 12/1,443,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,014
European (non-Finnish)	0.000939%	106,543

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: CDH15
Protein: p.Asp663=
Coding: c.1989C>T
MANE Select: NM_004933
dbSNP: rs769804850
Type: single nucleotide variant
Location: chr16:89193603 (GRCh38)
Gene constraint: LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 663: the 'disordered' region

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

Disease context

CDH15-related disorder

Similar variants

CDH15 p.Asp663Glu Uncertain significance ★ ⚠ same residue
CDH3 c.1796-2A>G Pathogenic ★★ same condition
CDH3 p.Arg103Ter Pathogenic ★★ same condition
CDH3 p.Arg503His Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDH3 p.Val205Met Likely pathogenic ★★ same condition
CDH3 p.Met269Thr Uncertain significance ★★ ⚠ same condition
CDH3 p.Glu289Ter Likely pathogenic ★ same condition
CDH15 p.Ala174Ser 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/cdh15-p-asp663 (accessed [today's date]).

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