Is CD99L2 p.Val202Ile (c.604G>A) pathogenic?

CD99L2 p.Val202Ile (c.604G>A) is classified Conflicting classifications of pathogenicity in CD99L2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-25). AlphaMissense: likely benign (0.1179); Ultra-rare (popmax 0.0961%, afr).

How common is CD99L2 p.Val202Ile (c.604G>A) in the general population?

CD99L2 p.Val202Ile (c.604G>A) is ultra-rare (popmax 0.0961%, afr) (gnomAD).

What do computational predictors say about CD99L2 p.Val202Ile (c.604G>A)?

AlphaMissense predicts likely benign (score 0.1179) — an in-silico prediction, not a clinical call.

CD99L2 p.Val202Ile

c.604G>A · rs150802524 · VCV2372869

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1179 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0961%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1179	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -10.00	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 3.3	GERP 0.1, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 130 kb · p 0.025 · regional, not allelic
Overall
CADD	22.4	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 0.0961% African / African-American · 55/57,252 alleles

Filtering AF 0.0758% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0685%

Overall 0.0367% 444/1,209,951 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0961%	1,041
Ashkenazi Jewishnot grpmax-eligible	0.0772%	1,295
European (non-Finnish)	0.039%	2,564
Remaining individualsnot grpmax-eligible	0.0252%	3,966
Admixed American	0.0196%	5,102
Finnishnot grpmax-eligible	0.00214%	46,623
South Asian	0.00176%	56,798

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.Val202Ile
Coding: c.604G>A
MANE Select: NM_031462
dbSNP: rs150802524
Type: single nucleotide variant
Location: chrX:150776225 (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-val202ile (accessed [today's date]).

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