NHS p.Ser665=
c.1995G>A · rs779565943 · VCV2660086
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, nfe)
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 -10 | GERP -5.8 |
| Overall | ||
| CADD | 0.016 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
European (non-Finnish) · 180/895,242 alleles
Filtering AF
0.0177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0167%
Overall
0.0163%
197/1,210,072 alleles · ultra-rare
exomes 189/1,098,248 · genomes 8/111,824 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0201% | 4,974 |
| Remaining individualsnot grpmax-eligible | 0.0126% | 7,934 |
| South Asian | 0.0088% | 11,362 |
| Admixed American | 0.00436% | 22,914 |
| Finnishnot grpmax-eligible | 0.00429% | 23,321 |
| African / African-American | 0.0035% | 28,549 |
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.Ser665=
- Coding
- c.1995G>A
- MANE Select
- NM_001291867
- dbSNP
- rs779565943
- Type
- single nucleotide variant
- Location
- chrX:17726101 (GRCh38)
- Structure
- AlphaFold pLDDT 43.65
- Residue 665
- the 'disordered' region
Similar variants
- NHS p.Ser665Leu Uncertain significance ★ 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
- NHS p.Ala745Val 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-ser665 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown