Is CD69 p.Cys96Arg (c.286T>C) pathogenic?

CD69 p.Cys96Arg (c.286T>C) is classified Uncertain significance in CD69 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely pathogenic (0.9367); Absent from gnomAD v4.1.

How common is CD69 p.Cys96Arg (c.286T>C) in the general population?

CD69 p.Cys96Arg (c.286T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD69 p.Cys96Arg (c.286T>C)?

AlphaMissense predicts likely pathogenic (score 0.9367) — an in-silico prediction, not a clinical call.

CD69 p.Cys96Arg

c.286T>C · VCV3998317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9367 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9367	likely pathogenic · top 3% in CD69
REVEL	0.385	indeterminate
SaProt	LLR -17.07	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,336 bp · p 0.033 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CD69
Protein: p.Cys96Arg
Coding: c.286T>C
MANE Select: NM_001781
Type: single nucleotide variant
Location: chr12:9755163 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 82.84 · 6 PDB
Residue 96: a β-strand; the c-type lectin domain; a disulfide bond

Full CD69 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD69 p.Lys177= Benign ★★ same type
CD69 p.Asn22Lys Uncertain significance ★ ⚠ same type
CD69 p.Asp171Asn Uncertain significance ★ ⚠ same type
CD69 p.Glu87Gly Uncertain significance ★ ⚠ same type
CD69 p.His151Tyr Uncertain significance ★ ⚠ same type
CD69 p.Pro40Ser Uncertain significance ★ ⚠ same type
CD69 p.Ser13Phe Uncertain significance ★ ⚠ same type
CD69 p.Ser182Ile 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/cd69-p-cys96arg (accessed [today's date]).

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