NANS p.Ser248=
c.744T>C · rs148983734 · VCV741408
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.693%, 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 -1.8 | GERP -4 |
| Overall | ||
| CADD | 7.539 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.693%
African / African-American · 519/74,896 alleles
Filtering AF
0.644%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.624%
Overall
0.0344%
555/1,613,824 alleles · rare
exomes 255/1,461,882 · genomes 300/151,942 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.693% | 144 |
| Remaining individualsnot grpmax-eligible | 0.032% | 3,125 |
| Admixed American | 0.0217% | 4,612 |
| European (non-Finnish) | 0.000254% | 393,326 |
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.Ser248=
- Coding
- c.744T>C
- MANE Select
- NM_018946
- dbSNP
- rs148983734
- Type
- single nucleotide variant
- Location
- chr9:98080956 (GRCh38)
- Gene constraint
- LOEUF 1.053 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.04 · 1 PDB
Similar variants
- 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
- NANS p.Lys358Arg 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-ser248 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown