NCL p.Asp242=
c.726T>C · rs116104217 · VCV778045
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.27%, afr)
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 -13 | GERP -3.1 |
| Overall | ||
| CADD | 0.003 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.27%
African / African-American · 953/74,910 alleles
Filtering AF
1.21%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.18%
Overall
0.0792%
1,278/1,613,298 alleles · low-frequency
exomes 723/1,461,250 · genomes 555/152,048 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.27% | 79 |
| Middle Eastern | 0.231% | 433 |
| Ashkenazi Jewishnot grpmax-eligible | 0.155% | 644 |
| Remaining individualsnot grpmax-eligible | 0.144% | 694 |
| Admixed American | 0.112% | 895 |
| European (non-Finnish) | 0.00882% | 11,341 |
| South Asian | 0.00439% | 22,762 |
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.Asp242=
- Coding
- c.726T>C
- MANE Select
- NM_005381
- dbSNP
- rs116104217
- Type
- single nucleotide variant
- Location
- chr2:231460754 (GRCh38)
- Gene constraint
- LOEUF 0.102 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.84 · 4 PDB
- Residue 242
- 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-asp242 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown