Is CD99L2 p.Pro87Arg (c.260C>G) pathogenic?

CD99L2 p.Pro87Arg (c.260C>G) is classified Uncertain significance in CD99L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.0954); Very rare (popmax 0.00157%, nfe).

How common is CD99L2 p.Pro87Arg (c.260C>G) in the general population?

CD99L2 p.Pro87Arg (c.260C>G) is very rare (popmax 0.00157%, nfe) (gnomAD).

What do computational predictors say about CD99L2 p.Pro87Arg (c.260C>G)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

CD99L2 p.Pro87Arg

c.260C>G · VCV3829672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00157%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.4, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 130 kb · p 0.025 · regional, not allelic
Overall
CADD	21.3	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 0.00157% European (non-Finnish) · 14/893,700 alleles

Filtering AF 0.000909% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000711%

Overall 0.00116% 14/1,207,885 alleles · very rare exomes 13/1,096,324 · genomes 1/111,561 · joint denominator

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.Pro87Arg
Coding: c.260C>G
MANE Select: NM_031462
Type: single nucleotide variant
Location: chrX:150814879 (GRCh38)
Structure: AlphaFold pLDDT 55.71
Residue 87: the 'disordered' region

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

Similar variants

CD99L2 p.Pro87Leu 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-pro87arg (accessed [today's date]).

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