Is CD63 p.Ile157Thr (c.470T>C) pathogenic?

CD63 p.Ile157Thr (c.470T>C) is classified Uncertain significance in CD63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: ambiguous (0.455); Very rare (popmax 0.00687%, nfe).

How common is CD63 p.Ile157Thr (c.470T>C) in the general population?

CD63 p.Ile157Thr (c.470T>C) is very rare (popmax 0.00687%, nfe) (gnomAD).

What do computational predictors say about CD63 p.Ile157Thr (c.470T>C)?

AlphaMissense predicts ambiguous (score 0.455) — an in-silico prediction, not a clinical call.

CD63 p.Ile157Thr

c.470T>C · VCV4222985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.455 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00687%, nfe)

Computational evidence

Protein change
AlphaMissense	0.455	ambiguous
REVEL	0.299	indeterminate
SaProt	LLR -7.94	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.5, phastCons 0.99
Regional constraint	o/e 0.84	unconstrained · MANE · 2,777 bp · p 0.0072 · regional, not allelic
Overall
CADD	19.81	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

Grpmax group 0.00687% European (non-Finnish) · 81/1,179,182 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00521% 84/1,611,786 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00687%	14,558
Remaining individualsnot grpmax-eligible	0.0048%	20,813

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: CD63
Protein: p.Ile157Thr
Coding: c.470T>C
MANE Select: NM_001780
Type: single nucleotide variant
Location: chr12:55726218 (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.Glu189Lys 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-ile157thr (accessed [today's date]).

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