Is CDH15 p.Asp185Glu (c.555C>G) pathogenic?

CDH15 p.Asp185Glu (c.555C>G) is classified Uncertain significance in CDH15 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-20). AlphaMissense: ambiguous (0.3744); Absent from gnomAD v4.1; Associated with CDH15-related disorder.

What condition is associated with CDH15 p.Asp185Glu (c.555C>G)?

CDH15 p.Asp185Glu (c.555C>G) is associated with CDH15-related disorder (ClinVar).

How common is CDH15 p.Asp185Glu (c.555C>G) in the general population?

CDH15 p.Asp185Glu (c.555C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH15 p.Asp185Glu (c.555C>G)?

AlphaMissense predicts ambiguous (score 0.3744) — an in-silico prediction, not a clinical call.

CDH15 p.Asp185Glu

c.555C>G · VCV3348241

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

CDH15-related disorder

Computational evidence

Protein change
AlphaMissense	0.3744	ambiguous
REVEL	0.074	moderately benign-leaning
SaProt	LLR -5.10	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	GERP 1.4, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 23 kb · p 5e-10 · regional, not allelic
Overall
CADD	15.8	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: CDH15
Protein: p.Asp185Glu
Coding: c.555C>G
MANE Select: NM_004933
Type: single nucleotide variant
Location: chr16:89185225 (GRCh38)
Gene constraint: LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 185: the cadherin 2 domain

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

Disease context

CDH15-related disorder

Similar variants

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
CDH15 p.Arg36Gln Conflicting classifications of pathogenicity ★ ⚠ 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-asp185glu (accessed [today's date]).

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