Is PARP9 p.Ala331Val (c.992C>T) pathogenic?

PARP9 p.Ala331Val (c.992C>T) is classified Uncertain significance in PARP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-28). AlphaMissense: likely benign (0.1099); Absent from gnomAD v4.1.

How common is PARP9 p.Ala331Val (c.992C>T) in the general population?

PARP9 p.Ala331Val (c.992C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PARP9 p.Ala331Val (c.992C>T)?

AlphaMissense predicts likely benign (score 0.1099) — an in-silico prediction, not a clinical call.

PARP9 p.Ala331Val

c.992C>T · rs2079293099 · VCV2298430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1099 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1099	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -7.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8	GERP -2
Regional constraint	o/e 0.79	unconstrained · MANE · 28 kb · p 1.1e-09 · regional, not allelic
Overall
CADD	4.993	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A366V vs ClinVar A331V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PARP9
Protein: p.Ala331Val
Coding: c.992C>T
MANE Select: NM_001146105
dbSNP: rs2079293099
Type: single nucleotide variant
Location: chr3:122552533 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.83 · 8 PDB
Residue 366 UniProt numbering: the macro 2 domain; an α-helix

Full PARP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PARP9 p.Asp795Glu Uncertain significance ★★ ⚠ same type
PARP9 p.Ile551Thr Uncertain significance ★★ ⚠ same type
PARP9 p.Tyr796Ser Uncertain significance ★★ ⚠ same type
PARP9 p.Glu405Lys Benign ★★ same type
PARP9 p.Thr616Ala Benign ★★ ⚠ same type
PARP9 c.49+10C>T Uncertain significance ★ ⚠ same type
PARP9 c.49+15C>T Uncertain significance ★ ⚠ same type
PARP9 c.49+21C>T 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/parp9-p-ala331val (accessed [today's date]).

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