NR5A1 p.Ala172=
c.516C>T · rs113506523 · VCV138537
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.57%, afr)
Conditions
2
spermatogenic failure 1
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 -5.1 | GERP -3.7 |
| Overall | ||
| CADD | 0.184 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.57%
African / African-American · 2,665/74,582 alleles
Filtering AF
3.46%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.41%
Overall
0.189%
2,993/1,583,304 alleles · low-frequency
exomes 1,461/1,431,014 · genomes 1,532/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.57% | 28 |
| Remaining individualsnot grpmax-eligible | 0.262% | 381 |
| Middle Eastern | 0.183% | 548 |
| Admixed American | 0.171% | 585 |
| South Asian | 0.00909% | 11,005 |
| European (non-Finnish) | 0.00454% | 22,010 |
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
- NR5A1
- Protein
- p.Ala172=
- Coding
- c.516C>T
- MANE Select
- NM_004959
- dbSNP
- rs113506523
- Type
- single nucleotide variant
- Location
- chr9:124500444 (GRCh38)
- Gene constraint
- LOEUF 0.314 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.83 · 6 PDB
- Residue 172
- a UniProt-annotated variant site (in srxy3; pathogenic)
Similar variants
- NR5A1 p.Arg313Cys Pathogenic/Likely pathogenic ★★ same condition
- NR5A1 p.Arg313His Pathogenic/Likely pathogenic ★★ same condition
- NR5A1 p.Arg69Gly Pathogenic/Likely pathogenic ★★ same condition
- NR5A1 p.Arg84Cys Pathogenic/Likely pathogenic ★★ same condition
- NR5A1 p.Arg84His Pathogenic/Likely pathogenic ★★ same condition
- NR5A1 p.Arg87Cys Pathogenic ★★ same condition
- NR5A1 p.Arg92Trp Pathogenic/Likely pathogenic ★★ same condition
- NR5A1 p.Gln112Ter Pathogenic ★★ 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/nr5a1-p-ala172 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown