Is PARP14 p.Glu1109Asp (c.3327A>C) pathogenic?

PARP14 p.Glu1109Asp (c.3327A>C) is classified Uncertain significance in PARP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). AlphaMissense: ambiguous (0.3854); Ultra-rare (popmax 0.0314%, eas).

How common is PARP14 p.Glu1109Asp (c.3327A>C) in the general population?

PARP14 p.Glu1109Asp (c.3327A>C) is ultra-rare (popmax 0.0314%, eas) (gnomAD).

What do computational predictors say about PARP14 p.Glu1109Asp (c.3327A>C)?

AlphaMissense predicts ambiguous (score 0.3854) — an in-silico prediction, not a clinical call.

PARP14 p.Glu1109Asp

c.3327A>C · rs750081986 · VCV2481500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3854 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0314%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3854	ambiguous
REVEL	0.12	moderately benign-leaning
SaProt	LLR -9.64	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 2, phastCons 0.99
Regional constraint	o/e 0.83	unconstrained · MANE · 47 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	17.98	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0314% East Asian · 14/44,654 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00101% 16/1,587,318 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0314%	3,190
Remaining individualsnot grpmax-eligible	0.00325%	30,814

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: PARP14
Protein: p.Glu1109Asp
Coding: c.3327A>C
MANE Select: NM_017554
dbSNP: rs750081986
Type: single nucleotide variant
Location: chr3:122704535 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.00 · 47 PDB
Residue 1109: the macro 2 domain; an α-helix

Full PARP14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PARP14 p.Pro1200Leu Uncertain significance ★★ ⚠ same type
PARP14 p.Ala1513Val Benign ★★ same type
PARP14 p.Ala864= Benign ★★ same type
PARP14 p.Asp488Asn Benign ★★ same type
PARP14 p.Gln1413Pro Benign ★★ same type
PARP14 p.Ala1187Ser Uncertain significance ★ ⚠ same type
PARP14 p.Ala1202Ser Uncertain significance ★ ⚠ same type
PARP14 p.Ala1350Asp 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/parp14-p-glu1109asp (accessed [today's date]).

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