Is CD63 p.Val216= (c.648C>T) pathogenic?

CD63 p.Val216= (c.648C>T) is classified Likely benign in CD63 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-13). Ultra-rare (popmax 0.0117%, amr).

How common is CD63 p.Val216= (c.648C>T) in the general population?

CD63 p.Val216= (c.648C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

CD63 p.Val216=

c.648C>T · VCV3829613

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

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 -0.47	GERP -3.1, phastCons 0.035
Overall
CADD	6.829	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,980 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.0018% 29/1,613,722 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,569
Remaining individualsnot grpmax-eligible	0.0048%	20,830
South Asian	0.00439%	22,763
African / African-American	0.00267%	37,472
European (non-Finnish)	0.0011%	90,755

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.Val216=
Coding: c.648C>T
MANE Select: NM_001780
Type: single nucleotide variant
Location: chr12:55725816 (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-val216 (accessed [today's date]).

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