NCL p.Asp198=
c.594C>T · rs572420764 · VCV726319
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0867%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.1 |
| Overall | ||
| CADD | 0.009 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0867%
Admixed American · 52/60,008 alleles
Filtering AF
0.0678%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0611%
Overall
0.00632%
102/1,613,276 alleles · ultra-rare
exomes 95/1,461,110 · genomes 7/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0867% | 1,154 |
| Middle Eastern | 0.0495% | 2,019 |
| African / African-American | 0.0107% | 9,372 |
| East Asian | 0.00669% | 14,954 |
| South Asian | 0.00549% | 18,205 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,830 |
| European (non-Finnish) | 0.00237% | 42,123 |
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
- NCL
- Protein
- p.Asp198=
- Coding
- c.594C>T
- MANE Select
- NM_005381
- dbSNP
- rs572420764
- Type
- single nucleotide variant
- Location
- chr2:231461559 (GRCh38)
- Gene constraint
- LOEUF 0.102 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.84 · 4 PDB
- Residue 198
- the 'disordered' region
Similar variants
- NCL p.Gly662Ser Uncertain significance ★★ same type
- NCL p.Ala629= Benign ★★ same type
- NCL p.Asp535= Benign ★★ same type
- NCL p.Glu196Asp Benign ★★ same type
- NCL p.Glu585= Benign ★★ same type
- NCL p.Lys116Thr Benign ★★ ⚠ same type
- NUCLEOLIN p.Ser328= Likely benign ★★ same type
- NCL p.Ala103Val 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/ncl-p-asp198 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown