NHS p.Asp1297=
c.3891C>T · rs761463158 · VCV281716
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0229%, mid)
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 -0.4 | GERP -4.6, phastCons 0.21 |
| Overall | ||
| CADD | 0.571 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0229%
Middle Eastern · 1/4,373 alleles
Filtering AF
0.000584%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000218%
Overall
0.00107%
13/1,209,581 alleles · ultra-rare
exomes 12/1,097,955 · genomes 1/111,626 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0229% | 4,373 |
| Remaining individualsnot grpmax-eligible | 0.0042% | 23,796 |
| South Asian | 0.00352% | 28,409 |
| Admixed American | 0.00219% | 45,696 |
| African / African-American | 0.00175% | 57,040 |
| European (non-Finnish) | 0.00067% | 149,172 |
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.Asp1297=
- Coding
- c.3891C>T
- MANE Select
- NM_001291867
- dbSNP
- rs761463158
- Type
- single nucleotide variant
- Location
- chrX:17727997 (GRCh38)
- Structure
- AlphaFold pLDDT 43.65
Similar variants
- NHS p.Asp1297Gly Benign/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
- 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-asp1297 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown