Is CD99 p.Arg180Pro (c.539G>C) pathogenic?

CD99 p.Arg180Pro (c.539G>C) is classified Uncertain significance in CD99 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). Ultra-rare (popmax 0.0165%, mid); Associated with CD99 Positive Neoplastic Cells Present.

What condition is associated with CD99 p.Arg180Pro (c.539G>C)?

CD99 p.Arg180Pro (c.539G>C) is associated with CD99 Positive Neoplastic Cells Present (ClinVar).

How common is CD99 p.Arg180Pro (c.539G>C) in the general population?

CD99 p.Arg180Pro (c.539G>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CD99 p.Arg180Pro

c.539G>C · rs150825051 · VCV634582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

CD99 Positive Neoplastic Cells Present

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.07	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP -1.4
Regional constraint	o/e 1.14	unconstrained · MANE · 49 kb · p 0.03 · regional, not allelic
Overall
CADD	12.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,054 alleles

Overall 6.84e-05% 1/1,461,642 alleles · ultra-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: CD99
Protein: p.Arg180Pro
Coding: c.539G>C
MANE Select: NM_002414
dbSNP: rs150825051
Type: single nucleotide variant
Location: chrX:2740785 (GRCh38)
Structure: AlphaFold pLDDT 60.43 · 1 PDB
Residue 180: the 'disordered' region

Full CD99 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CD99 Positive Neoplastic Cells Present — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD99 p.Asp66Glu Likely benign ★ 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/cd99-p-arg180pro (accessed [today's date]).

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