Is CD99L2 p.Asn129Asp (c.385A>G) pathogenic?

CD99L2 p.Asn129Asp (c.385A>G) is classified Uncertain significance in CD99L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-07). AlphaMissense: ambiguous (0.3735); Very rare (popmax 0.000182%).

How common is CD99L2 p.Asn129Asp (c.385A>G) in the general population?

CD99L2 p.Asn129Asp (c.385A>G) is very rare (popmax 0.000182%) (gnomAD).

What do computational predictors say about CD99L2 p.Asn129Asp (c.385A>G)?

AlphaMissense predicts ambiguous (score 0.3735) — an in-silico prediction, not a clinical call.

CD99L2 p.Asn129Asp

c.385A>G · rs1557419864 · VCV2270761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000182%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3735	ambiguous
REVEL	0.051	moderately benign-leaning
SaProt	LLR -3.79	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 2, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 130 kb · p 0.025 · regional, not allelic
Overall
CADD	15.86	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 0.000182%

Overall 0.000182% 2/1,098,206 alleles · very 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: CD99L2
Protein: p.Asn129Asp
Coding: c.385A>G
MANE Select: NM_031462
dbSNP: rs1557419864
Type: single nucleotide variant
Location: chrX:150795251 (GRCh38)
Structure: AlphaFold pLDDT 55.71
Residue 129: the 'disordered' region

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-asn129asp (accessed [today's date]).

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