Is PARP9 p.Phe352Ser (c.1055T>C) pathogenic?

PARP9 p.Phe352Ser (c.1055T>C) is classified Likely benign in PARP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely benign (0.0419); Very rare (popmax 8.47e-05%, nfe).

How common is PARP9 p.Phe352Ser (c.1055T>C) in the general population?

PARP9 p.Phe352Ser (c.1055T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PARP9 p.Phe352Ser (c.1055T>C)?

AlphaMissense predicts likely benign (score 0.0419) — an in-silico prediction, not a clinical call.

PARP9 p.Phe352Ser

c.1055T>C · VCV3885787

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0419 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0419	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -3.57	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 0.28	GERP -2.7, phastCons 0.003
Regional constraint	o/e 0.79	unconstrained · MANE · 28 kb · p 1.1e-09 · regional, not allelic
Overall
CADD	0.724	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 F387S vs ClinVar F352S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,018 alleles

Overall 0.000657% 1/152,204 alleles · very rare

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: PARP9
Protein: p.Phe352Ser
Coding: c.1055T>C
MANE Select: NM_001146105
Type: single nucleotide variant
Location: chr3:122552470 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.83 · 8 PDB
Residue 387 UniProt numbering: the macro 2 domain; a β-strand

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-phe352ser (accessed [today's date]).

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