Is CD63 p.Arg108Ser (c.324A>T) pathogenic?

CD63 p.Arg108Ser (c.324A>T) is classified Uncertain significance in CD63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.7565); Absent from gnomAD v4.1.

How common is CD63 p.Arg108Ser (c.324A>T) in the general population?

CD63 p.Arg108Ser (c.324A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD63 p.Arg108Ser (c.324A>T)?

AlphaMissense predicts likely pathogenic (score 0.7565) — an in-silico prediction, not a clinical call.

CD63 p.Arg108Ser

c.324A>T · VCV4222986

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7565 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7565	likely pathogenic
REVEL	0.682	pathogenic-leaning
SaProt	LLR -8.38	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,777 bp · p 0.0072 · regional, not allelic
Overall
CADD	24.9	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.Arg108Ser
Coding: c.324A>T
MANE Select: NM_001780
Type: single nucleotide variant
Location: chr12:55726896 (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.Arg164Gln Uncertain significance ★ ⚠ same type
CD63 p.Asn130His Uncertain significance ★ ⚠ same type
CD63 p.Gln122His Uncertain significance ★ ⚠ same type
CD63 p.Glu189Lys 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-arg108ser (accessed [today's date]).

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