NANS p.Ser253=
c.759G>A · VCV4771277
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00768%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -4 |
| Overall | ||
| CADD | 0.026 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00768%
South Asian · 7/91,090 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.00161%
26/1,614,054 alleles · very rare
exomes 23/1,461,876 · genomes 3/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00768% | 13,013 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,620 |
| African / African-American | 0.004% | 24,973 |
| East Asian | 0.00223% | 44,894 |
| Admixed American | 0.00167% | 60,004 |
| European (non-Finnish) | 0.000847% | 118,004 |
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.Ser253=
- Coding
- c.759G>A
- MANE Select
- NM_018946
- Type
- single nucleotide variant
- Location
- chr9:98080971 (GRCh38)
- Gene constraint
- LOEUF 1.053 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.04 · 1 PDB
Similar variants
- NANS p.Ser253Leu 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-ser253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown