Is CD69 p.Ser182Ile (c.545G>T) pathogenic?

CD69 p.Ser182Ile (c.545G>T) is classified Uncertain significance in CD69 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.1809); Ultra-rare (popmax 0.0879%, sas).

How common is CD69 p.Ser182Ile (c.545G>T) in the general population?

CD69 p.Ser182Ile (c.545G>T) is ultra-rare (popmax 0.0879%, sas) (gnomAD).

What do computational predictors say about CD69 p.Ser182Ile (c.545G>T)?

AlphaMissense predicts likely benign (score 0.1809) — an in-silico prediction, not a clinical call.

CD69 p.Ser182Ile

c.545G>T · VCV4222998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1809 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0879%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1809	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -9.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP -1.9, phastCons 0.011
Regional constraint	o/e 0.86	unconstrained · MANE · 7,336 bp · p 0.033 · regional, not allelic
Overall
CADD	15.87	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 0.0879% South Asian · 79/89,916 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0665%

Overall 0.00515% 82/1,591,734 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0879%	1,138
Remaining individualsnot grpmax-eligible	0.00486%	20,578

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: CD69
Protein: p.Ser182Ile
Coding: c.545G>T
MANE Select: NM_001781
Type: single nucleotide variant
Location: chr12:9753536 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 82.84 · 6 PDB
Residue 182: a disulfide bond; a β-strand; the c-type lectin domain

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-ser182ile (accessed [today's date]).

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