Is CD63 p.Val70Met (c.208G>A) pathogenic?

CD63 p.Val70Met (c.208G>A) is classified Uncertain significance in CD63 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: likely benign (0.2383); Very rare (popmax 0.000593%, nfe).

How common is CD63 p.Val70Met (c.208G>A) in the general population?

CD63 p.Val70Met (c.208G>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CD63 p.Val70Met (c.208G>A)?

AlphaMissense predicts likely benign (score 0.2383) — an in-silico prediction, not a clinical call.

CD63 p.Val70Met

c.208G>A · VCV3488146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2383 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2383	likely benign
REVEL	0.418	indeterminate
SaProt	LLR -5.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP 0.93, phastCons 0.029
Regional constraint	o/e 0.84	unconstrained · MANE · 2,777 bp · p 0.0072 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,180,024 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,576 alleles · very rare

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.Val70Met
Coding: c.208G>A
MANE Select: NM_001780
Type: single nucleotide variant
Location: chr12:55727198 (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-val70met (accessed [today's date]).

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