NUS1 p.Pro193=
c.579G>A · rs753713015 · VCV965784
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
Conditions
1
congenital disorder of glycosylation, type Iaa
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 0.92 | GERP -0.97, phastCons 0.98 |
| Overall | ||
| CADD | 8.571 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/59,838 alleles
Filtering AF
0.00545%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.00143%
23/1,611,238 alleles · ultra-rare
exomes 22/1,459,270 · genomes 1/151,968 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,548 |
| South Asian | 0.0066% | 15,141 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,290 |
| African / African-American | 0.00134% | 74,744 |
| European (non-Finnish) | 0.000679% | 147,363 |
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
- NUS1
- Protein
- p.Pro193=
- Coding
- c.579G>A
- MANE Select
- NM_138459
- dbSNP
- rs753713015
- Type
- single nucleotide variant
- Location
- chr6:117694068 (GRCh38)
- Gene constraint
- LOEUF 0.182 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.01 · 9 PDB
- Residue 193
- a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; likely pathogenic); an α-helix
Similar variants
- NUS1 p.Pro193Ala Uncertain significance ★ ⚠ same residue
- NUS1 p.Pro193Leu Likely benign ★ same residue
- NUS1 c.415+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NUS1 c.692-2A>G Likely pathogenic ★★ same condition
- NUS1 p.Arg290Cys Pathogenic/Likely pathogenic ★★ same condition
- NUS1 p.Leu240Ter Pathogenic/Likely pathogenic ★★ same condition
- NUS1 p.Ala44Thr Uncertain significance ★★ ⚠ same condition
- NUS1 p.Ala79Val Uncertain significance ★★ ⚠ same condition
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/nus1-p-pro193 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown