NPC2 c.*252del
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.43%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.55 | GERP -0.65, phastCons 0.001 |
| Non-coding constraint | Z 1.78 | 1 kb window · o/e 0.87 · regional · uncalibrated |
| Overall | ||
| CADD | 1.108 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.43%
African / African-American · 966/67,548 alleles
Filtering AF
1.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.33%
Overall
0.139%
1,914/1,373,998 alleles · low-frequency
exomes 1,315/1,224,194 · genomes 599/149,804 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.43% | 70 |
| Admixed American | 0.237% | 421 |
| Remaining individualsnot grpmax-eligible | 0.213% | 469 |
| East Asian | 0.198% | 504 |
| Middle Eastern | 0.169% | 592 |
| Finnishnot grpmax-eligible | 0.167% | 599 |
| Ashkenazi Jewishnot grpmax-eligible | 0.12% | 831 |
| South Asian | 0.0872% | 1,146 |
| European (non-Finnish) | 0.0497% | 2,013 |
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
- NPC2
- Coding
- c.*252del
- MANE Select
- NM_006432
- dbSNP
- rs369932535
- Type
- Deletion
- Location
- chr14:74480022 (GRCh38)
- Gene constraint
- LOEUF 1.422 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.88 · 2 PDB
Similar variants
- NPC2 c.191-1_193del Likely pathogenic ★ same type
- NPC2 p.Ala5fs Pathogenic ★ same type
- NPC2 p.Asn111fs Pathogenic ★ same type
- NPC2 p.Asp31fs Likely pathogenic ★ same type
- NPC2 p.Ile97fs Pathogenic ★ same type
- NPC2 p.Ser50fs Likely pathogenic ★ same type
- NPC2 p.Thr44fs Pathogenic ★ same type
- NPC2 p.Thr62fs Likely pathogenic ★ 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/npc2-c-star-252del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown