NHS p.Arg204=
c.612C>T · rs777799752 · VCV753812
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0218%, 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.8 | GERP -3.8 |
| Overall | ||
| CADD | 0.445 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0218%
Admixed American · 10/45,849 alleles
Filtering AF
0.0118%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00899%
Overall
0.0019%
23/1,210,251 alleles · ultra-rare
exomes 22/1,098,146 · genomes 1/112,105 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0218% | 4,585 |
| African / African-American | 0.00175% | 57,158 |
| European (non-Finnish) | 0.00134% | 74,605 |
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.Arg204=
- Coding
- c.612C>T
- MANE Select
- NM_001291867
- dbSNP
- rs777799752
- Type
- single nucleotide variant
- Location
- chrX:17687788 (GRCh38)
- Structure
- AlphaFold pLDDT 43.65
- Residue 204
- the 'wave homology domain (whd)' region
Similar variants
- NHS p.Arg204His Uncertain significance ★★ same residue
- NHS p.Arg204Cys Likely benign ★ same residue
- 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
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-arg204 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown