Is CD99L2 p.Arg169Trp (c.505C>T) pathogenic?

CD99L2 p.Arg169Trp (c.505C>T) is classified Uncertain significance in CD99L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely benign (0.1276); Very rare (popmax 0.00698%, afr).

How common is CD99L2 p.Arg169Trp (c.505C>T) in the general population?

CD99L2 p.Arg169Trp (c.505C>T) is very rare (popmax 0.00698%, afr) (gnomAD).

What do computational predictors say about CD99L2 p.Arg169Trp (c.505C>T)?

AlphaMissense predicts likely benign (score 0.1276) — an in-silico prediction, not a clinical call.

CD99L2 p.Arg169Trp

c.505C>T · VCV3264913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1276 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00698%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1276	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -10.25	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.59	GERP -3
Regional constraint	o/e 1.15	unconstrained · MANE · 130 kb · p 0.025 · regional, not allelic
Overall
CADD	16.28	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

Grpmax group 0.00698% African / African-American · 4/57,309 alleles

Filtering AF 0.00233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.00215% 26/1,209,598 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00698%	14,327
Admixed American	0.00438%	22,835
Remaining individualsnot grpmax-eligible	0.0021%	47,588
European (non-Finnish)	0.00201%	49,724
South Asian	0.00176%	56,698

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: CD99L2
Protein: p.Arg169Trp
Coding: c.505C>T
MANE Select: NM_031462
Type: single nucleotide variant
Location: chrX:150777474 (GRCh38)
Structure: AlphaFold pLDDT 55.71
Residue 169: the 'disordered' region

Full CD99L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD99L2 p.Arg169Gln Uncertain significance ★ ⚠ same residue
CD99L2 p.Asp175Asn Benign/Likely benign ★★ same type
CD99L2 c.203-9C>A Uncertain significance ★ same type
CD99L2 c.68-5755G>T Uncertain significance ★ same type
CD99L2 p.Ala182Ser Uncertain significance ★ ⚠ same type
CD99L2 p.Arg104Lys Uncertain significance ★ ⚠ same type
CD99L2 p.Arg131Gln Uncertain significance ★ ⚠ same type
CD99L2 p.Arg135Cys 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/cd99l2-p-arg169trp (accessed [today's date]).

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