YY1AP1 p.Ala591=
c.1773C>T · rs397834368 · VCV709137
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0726%, nfe)
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 0.01 | GERP -2.3, phastCons 0.38 |
| Overall | ||
| CADD | 12.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0726%
European (non-Finnish) · 856/1,178,990 alleles
Filtering AF
0.0685%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0669%
Overall
0.0571%
921/1,613,128 alleles · ultra-rare
exomes 836/1,460,802 · genomes 85/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0726% | 1,377 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,717 |
| African / African-American | 0.0187% | 5,360 |
| Admixed American | 0.0167% | 6,003 |
| South Asian | 0.0165% | 6,071 |
| East Asian | 0.00446% | 22,444 |
| Finnishnot grpmax-eligible | 0.00156% | 64,040 |
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
- YY1AP1
- Protein
- p.Ala591=
- Coding
- c.1773C>T
- MANE Select
- NM_139119
- dbSNP
- rs397834368
- Type
- single nucleotide variant
- Location
- chr1:155660137 (GRCh38)
- Gene constraint
- LOEUF 1.319 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.58
- Residue 591
- a UniProt-annotated variant site (in grng)
Similar variants
- YY1AP1 c.412-1G>A Pathogenic ★★ same type
- YY1AP1 p.Gln84Ter Pathogenic/Likely pathogenic ★★ same type
- YY1AP1 p.Gln75His Uncertain significance ★★ ⚠ same type
- YY1AP1 p.Ile135Met Uncertain significance ★★ ⚠ same type
- YY1AP1 c.324+7C>T Likely benign ★★ same type
- YY1AP1 p.Ala579= Benign ★★ same type
- YY1AP1 p.Gln435Arg Benign ★★ same type
- YY1AP1 p.His325= Likely benign ★★ same type
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/yy1ap1-p-ala591 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown