Is CD99L2 p.Arg261Gln (c.782G>A) pathogenic?

CD99L2 p.Arg261Gln (c.782G>A) is classified Conflicting classifications of pathogenicity in CD99L2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-27). AlphaMissense: likely benign (0.0913); Ultra-rare (popmax 0.0809%, sas).

How common is CD99L2 p.Arg261Gln (c.782G>A) in the general population?

CD99L2 p.Arg261Gln (c.782G>A) is ultra-rare (popmax 0.0809%, sas) (gnomAD).

What do computational predictors say about CD99L2 p.Arg261Gln (c.782G>A)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

CD99L2 p.Arg261Gln

c.782G>A · rs374932537 · VCV764770

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0809%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -5.26	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 0.13	GERP -0.52, phastCons 0.14
Regional constraint	o/e 1.15	unconstrained · MANE · 130 kb · p 0.025 · regional, not allelic
Overall
CADD	15.34	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 0.0809% South Asian · 39/48,186 alleles

Filtering AF 0.0608% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0538%

Overall 0.00765% 88/1,149,669 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0809%	1,236
Middle Eastern	0.0244%	4,096
African / African-American	0.0132%	7,582
Admixed American	0.00646%	15,486
Remaining individualsnot grpmax-eligible	0.00444%	22,539
European (non-Finnish)	0.00412%	24,273
East Asian	0.00336%	29,728

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.Arg261Gln
Coding: c.782G>A
MANE Select: NM_031462
dbSNP: rs374932537
Type: single nucleotide variant
Location: chrX:150769041 (GRCh38)
Structure: AlphaFold pLDDT 55.71

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

Similar variants

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
CD99L2 p.Arg169Gln 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-arg261gln (accessed [today's date]).

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