Is CD69 p.Val39Asp (c.116T>A) pathogenic?

CD69 p.Val39Asp (c.116T>A) is classified Uncertain significance in CD69 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). AlphaMissense: ambiguous (0.431); Absent from gnomAD v4.1.

How common is CD69 p.Val39Asp (c.116T>A) in the general population?

CD69 p.Val39Asp (c.116T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD69 p.Val39Asp (c.116T>A)?

AlphaMissense predicts ambiguous (score 0.431) — an in-silico prediction, not a clinical call.

CD69 p.Val39Asp

c.116T>A · VCV3829621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.431 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.431	ambiguous
REVEL	0.271	benign-leaning
SaProt	LLR -8.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,336 bp · p 0.033 · regional, not allelic
Overall
CADD	23.2	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: CD69
Protein: p.Val39Asp
Coding: c.116T>A
MANE Select: NM_001781
Type: single nucleotide variant
Location: chr12:9756368 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 82.84 · 6 PDB

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.Cys96Arg 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

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-val39asp (accessed [today's date]).

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