NHS p.Arg274=
c.822G>A · rs1192420369 · VCV1027922
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00218%, amr)
Conditions
1
Nance-Horan syndrome
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 0.85 | GERP -0.21, phastCons 1 |
| Overall | ||
| CADD | 9.588 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00218%
Admixed American · 1/45,888 alleles
Overall
8.26e-05%
1/1,210,541 alleles · very rare
exomes 1/1,098,101 · genomes 0/112,440 · joint denominator
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.Arg274=
- Coding
- c.822G>A
- MANE Select
- NM_001291867
- dbSNP
- rs1192420369
- Type
- single nucleotide variant
- Location
- chrX:17692438 (GRCh38)
- Structure
- AlphaFold pLDDT 43.65
- Residue 274
- the 'disordered' region
Similar variants
- NHS p.Arg248Ter Pathogenic ★★ same condition
- NHS p.Arg394Ter Pathogenic ★★ same condition
- NHS p.Arg900Ter Pathogenic ★★ same condition
- NHS p.Gln411Ter Pathogenic ★★ same condition
- NHS p.Gln80Ter Pathogenic/Likely pathogenic ★★ same condition
- NHS p.Ala564Val Uncertain significance ★★ same condition
- NHS p.Ala745Val Uncertain significance ★★ same condition
- NHS p.Arg162Cys 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/nhs-p-arg274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown