Is CD69 p.Lys177= (c.531A>G) pathogenic?

CD69 p.Lys177= (c.531A>G) is classified Benign in CD69 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-07). Rare (popmax 0.763%, sas).

How common is CD69 p.Lys177= (c.531A>G) in the general population?

CD69 p.Lys177= (c.531A>G) is rare (popmax 0.763%, sas) (gnomAD).

CD69 p.Lys177=

c.531A>G · rs117419783 · VCV769384

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.763%, sas)

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 -0.16	GERP -3.7
Overall
CADD	0.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.763% South Asian · 684/89,620 alleles

Filtering AF 0.716% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.697%

Overall 0.601% 9,549/1,589,790 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.96%	104
South Asiangrpmax	0.763%	131
European (non-Finnish)	0.659%	152
Remaining individualsnot grpmax-eligible	0.55%	182
Middle Eastern	0.367%	273
Admixed American	0.248%	403
African / African-American	0.122%	818
Ashkenazi Jewishnot grpmax-eligible	0.0272%	3,680
East Asian	0.0045%	22,242

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys177=
Coding: c.531A>G
MANE Select: NM_001781
dbSNP: rs117419783
Type: single nucleotide variant
Location: chr12:9753550 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 82.84 · 6 PDB
Residue 177: 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.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
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-lys177 (accessed [today's date]).

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