NANS p.Pro302=
c.906G>A · rs748375515 · VCV2993398
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -0.37 | GERP -4.6 |
| Overall | ||
| CADD | 9.997 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.000738%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000805%
13/1,614,020 alleles · ultra-rare
exomes 11/1,461,872 · genomes 2/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| East Asian | 0.00445% | 22,448 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| South Asian | 0.0022% | 45,544 |
| European (non-Finnish) | 0.000508% | 196,674 |
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
- NANS
- Protein
- p.Pro302=
- Coding
- c.906G>A
- MANE Select
- NM_018946
- dbSNP
- rs748375515
- Type
- single nucleotide variant
- Location
- chr9:98082881 (GRCh38)
- Gene constraint
- LOEUF 1.053 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.04 · 1 PDB
- Residue 302
- the afp-like domain
Similar variants
- NANS p.Pro302Leu Uncertain significance ★ ⚠ same residue
- NANS c.448+1G>A Pathogenic/Likely pathogenic ★★ same type
- NANS p.Glu258Ter Pathogenic/Likely pathogenic ★★ same type
- NANS p.Ala102Thr Uncertain significance ★★ ⚠ same type
- NANS p.Arg264Gln Uncertain significance ★★ ⚠ same type
- NANS p.Arg267His Uncertain significance ★★ same type
- NANS p.Gln94Glu Uncertain significance ★★ ⚠ same type
- NANS p.Ile301Met 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/nans-p-pro302 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown