Is PARP2 p.Arg277Pro (c.830G>C) pathogenic?

PARP2 p.Arg277Pro (c.830G>C) is classified Uncertain significance in PARP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). AlphaMissense: likely pathogenic (0.6307); Very rare (popmax 0.00178%, nfe).

How common is PARP2 p.Arg277Pro (c.830G>C) in the general population?

PARP2 p.Arg277Pro (c.830G>C) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about PARP2 p.Arg277Pro (c.830G>C)?

AlphaMissense predicts likely pathogenic (score 0.6307) — an in-silico prediction, not a clinical call.

PARP2 p.Arg277Pro

c.830G>C · VCV3304396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6307 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6307	likely pathogenic
REVEL	0.137	moderately benign-leaning
SaProt	LLR -13.57	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP 0.026, phastCons 0.51
Regional constraint	o/e 0.94	unconstrained · MANE · 14 kb · p 0.15 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R290P vs ClinVar R277P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,179,918 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,613,746 alleles · very rare exomes 19/1,461,744 · genomes 2/152,002 · joint denominator

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.Arg277Pro
Coding: c.830G>C
MANE Select: NM_001042618
Type: single nucleotide variant
Location: chr14:20354875 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.82 · 30 PDB
Residue 290 UniProt numbering: the parp alpha-helical domain; an α-helix

Full PARP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-arg277pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown