NHS p.Pro83=
c.249G>T · rs1240476811 · VCV440007
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0702%, mid)
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 0.84 | GERP -1.1, phastCons 0.01 |
| Overall | ||
| CADD | 6.712 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0702%
Middle Eastern · 2/2,850 alleles
Filtering AF
0.0124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.00037%
4/1,081,117 alleles · ultra-rare
exomes 2/969,795 · genomes 2/111,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0702% | 1,425 |
| African / African-American | 0.00389% | 25,718 |
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
- NHS
- Protein
- p.Pro83=
- Coding
- c.249G>T
- MANE Select
- NM_001291867
- dbSNP
- rs1240476811
- Type
- single nucleotide variant
- Location
- chrX:17376006 (GRCh38)
- Structure
- AlphaFold pLDDT 43.65
- Residue 83
- the 'wave homology domain (whd)' region; the 'disordered' region
Similar variants
- NHS p.Arg248Ter Pathogenic ★★ same type
- NHS p.Arg394Ter Pathogenic ★★ same type
- NHS p.Arg900Ter Pathogenic ★★ same type
- NHS p.Gln411Ter Pathogenic ★★ same type
- NHS p.Gln80Ter Pathogenic/Likely pathogenic ★★ same type
- NHS p.Ala564Val Uncertain significance ★★ same type
- NHS p.Ala745Val Uncertain significance ★★ same type
- NHS p.Arg162Cys 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/nhs-p-pro83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown