NCL p.Asp247=
c.741C>T · rs144584882 · VCV753947
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0174%, 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 -20 | GERP -3 |
| Overall | ||
| CADD | 0.006 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0174%
African / African-American · 13/74,632 alleles
Filtering AF
0.0103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00816%
Overall
0.00298%
48/1,609,006 alleles · ultra-rare
exomes 34/1,457,282 · genomes 14/151,724 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0174% | 5,741 |
| Admixed American | 0.00667% | 14,981 |
| Finnishnot grpmax-eligible | 0.00313% | 31,968 |
| European (non-Finnish) | 0.00238% | 41,993 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,356 |
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.Asp247=
- Coding
- c.741C>T
- MANE Select
- NM_005381
- dbSNP
- rs144584882
- Type
- single nucleotide variant
- Location
- chr2:231460739 (GRCh38)
- Gene constraint
- LOEUF 0.102 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.84 · 4 PDB
- Residue 247
- 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-asp247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown