PARP2 p.Ala159=
c.477C>T · rs749880083 · VCV727595
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.27 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.22 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP 0.88, phastCons 1 |
| Overall | ||
| CADD | 9.418 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
African / African-American · 21/74,954 alleles
Filtering AF
0.0187%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00136%
22/1,613,566 alleles · ultra-rare
exomes 9/1,461,432 · genomes 13/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.028% | 3,569 |
| Admixed American | 0.00167% | 59,992 |
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
- PARP2
- Protein
- p.Ala159=
- Coding
- c.477C>T
- MANE Select
- NM_001042618
- dbSNP
- rs749880083
- Type
- single nucleotide variant
- Location
- chr14:20351102 (GRCh38)
- Gene constraint
- LOEUF 1.037 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.82 · 30 PDB
- Residue 159
- the wgr domain; a β-strand
Similar variants
- PARP2 p.Asp222Gly Benign ★★ ⚠ same type
- PARP2 p.Leu345= Benign ★★ same type
- PARP2 p.Ser148Asn Benign ★★ same type
- PARP2 c.202+13G>A Uncertain significance ★ ⚠ same type
- PARP2 c.202+22C>T Uncertain significance ★ ⚠ same type
- PARP2 c.202+37C>G Uncertain significance ★ ⚠ same type
- PARP2 p.Ala14Thr Uncertain significance ★ ⚠ same type
- PARP2 p.Ala323Ser Uncertain significance ★ ⚠ 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/parp2-p-ala159 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown