Is CD99L2 p.Asp82His (c.244G>C) pathogenic?

CD99L2 p.Asp82His (c.244G>C) is classified Uncertain significance in CD99L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: likely benign (0.1066); Very rare (popmax 0.00592%, nfe).

How common is CD99L2 p.Asp82His (c.244G>C) in the general population?

CD99L2 p.Asp82His (c.244G>C) is very rare (popmax 0.00592%, nfe) (gnomAD).

What do computational predictors say about CD99L2 p.Asp82His (c.244G>C)?

AlphaMissense predicts likely benign (score 0.1066) — an in-silico prediction, not a clinical call.

CD99L2 p.Asp82His

c.244G>C · VCV3998401

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1066 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00592%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1066	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -10.41	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 0.068	GERP 0.45
Regional constraint	o/e 1.15	unconstrained · MANE · 130 kb · p 0.025 · regional, not allelic
Overall
CADD	15.56	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 0.00592% European (non-Finnish) · 53/894,970 alleles

Filtering AF 0.00462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00419%

Overall 0.00463% 56/1,209,567 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00592%	16,886
Admixed American	0.00219%	45,694
Remaining individualsnot grpmax-eligible	0.0021%	47,580
African / African-American	0.00175%	57,136

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.Asp82His
Coding: c.244G>C
MANE Select: NM_031462
Type: single nucleotide variant
Location: chrX:150814895 (GRCh38)
Structure: AlphaFold pLDDT 55.71
Residue 82: 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-asp82his (accessed [today's date]).

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