NCL p.Asp535=
c.1605C>T · rs61754797 · VCV712368
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.48%, 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 1.5 | GERP -3.1, phastCons 1 |
| Overall | ||
| CADD | 13.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.48%
African / African-American · 1,109/75,014 alleles
Filtering AF
1.41%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.38%
Overall
0.197%
3,175/1,614,076 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.48% | 68 |
| Middle Eastern | 1.17% | 85 |
| Admixed American | 0.587% | 170 |
| Remaining individualsnot grpmax-eligible | 0.4% | 250 |
| Ashkenazi Jewishnot grpmax-eligible | 0.382% | 262 |
| European (non-Finnish) | 0.105% | 952 |
| South Asian | 0.034% | 2,938 |
| East Asian | 0.00891% | 11,219 |
| Finnishnot grpmax-eligible | 0.00781% | 12,801 |
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.Asp535=
- Coding
- c.1605C>T
- MANE Select
- NM_005381
- dbSNP
- rs61754797
- Type
- single nucleotide variant
- Location
- chr2:231456731 (GRCh38)
- Gene constraint
- LOEUF 0.102 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.84 · 4 PDB
- Residue 535
- the rrm 3 domain; an α-helix
Similar variants
- NCL p.Gly662Ser Uncertain significance ★★ same type
- NCL p.Ala629= 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
- NCL p.Ala134Ser 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-asp535 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown