Is CD63 p.Glu189Lys (c.565G>A) pathogenic?

CD63 p.Glu189Lys (c.565G>A) is classified Uncertain significance in CD63 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.2057); Absent from gnomAD v4.1.

How common is CD63 p.Glu189Lys (c.565G>A) in the general population?

CD63 p.Glu189Lys (c.565G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD63 p.Glu189Lys (c.565G>A)?

AlphaMissense predicts likely benign (score 0.2057) — an in-silico prediction, not a clinical call.

CD63 p.Glu189Lys

c.565G>A · rs2540183619 · VCV3140645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2057 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2057	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -10.03	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.96 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.2	GERP -3.3
Regional constraint	o/e 0.84	unconstrained · MANE · 2,777 bp · p 0.0072 · regional, not allelic
Overall
CADD	5.001	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: CD63
Protein: p.Glu189Lys
Coding: c.565G>A
MANE Select: NM_001780
dbSNP: rs2540183619
Type: single nucleotide variant
Location: chr12:55726123 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 2 PDB

Full CD63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD63 c.426+9G>C Benign ★★ same type
CD63 p.Asn129= Benign ★★ same type
RDH5 c.570-8G>C Benign/Likely benign ★★ same type
CD63 p.Arg108Ser Uncertain significance ★ ⚠ same type
CD63 p.Arg164Gln Uncertain significance ★ ⚠ same type
CD63 p.Asn130His Uncertain significance ★ ⚠ same type
CD63 p.Gln122His Uncertain significance ★ ⚠ same type
CD63 p.Glu217Lys Uncertain significance ★ ⚠ 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/cd63-p-glu189lys (accessed [today's date]).

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