NCL p.Thr92Pro
c.274A>C · VCV3917979
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.1191 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1191 | likely benign |
|---|---|---|
| REVEL | 0.132 | moderately benign-leaning |
| SaProt | LLR -11.22 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense and REVEL do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.49 | GERP -3.5 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 6,682 bp · p 0.41 · regional, not allelic |
| Overall | ||
| CADD | 12.81 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- NCL
- Protein
- p.Thr92Pro
- Coding
- c.274A>C
- MANE Select
- NM_005381
- Type
- single nucleotide variant
- Location
- chr2:231461879 (GRCh38)
- Gene constraint
- LOEUF 0.102 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.84 · 4 PDB
- Residue 92
- the 'disordered' region; the '8 x 8 aa tandem repeats of x-t-p-x-k-k-x-x' region; a modified residue (phosphothreonine)
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-thr92pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown