Is PARP14 p.Cys1295Phe (c.3884G>T) pathogenic?

PARP14 p.Cys1295Phe (c.3884G>T) is classified Uncertain significance in PARP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). AlphaMissense: likely pathogenic (0.842); Very rare (popmax 8.5e-05%, nfe).

How common is PARP14 p.Cys1295Phe (c.3884G>T) in the general population?

PARP14 p.Cys1295Phe (c.3884G>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about PARP14 p.Cys1295Phe (c.3884G>T)?

AlphaMissense predicts likely pathogenic (score 0.842) — an in-silico prediction, not a clinical call.

PARP14 p.Cys1295Phe

c.3884G>T · rs2473340826 · VCV3208725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.842 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.842	likely pathogenic · top 7% in PARP14
REVEL	0.595	indeterminate
SaProt	LLR -11.13	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.62 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.4	GERP 2.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 47 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,175,904 alleles

Overall 6.25e-05% 1/1,600,970 alleles · very rare exomes 1/1,448,822 · genomes 0/152,148 · 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: PARP14
Protein: p.Cys1295Phe
Coding: c.3884G>T
MANE Select: NM_017554
dbSNP: rs2473340826
Type: single nucleotide variant
Location: chr3:122714313 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.00 · 47 PDB
Residue 1295: the macro 3 domain; a β-strand

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-cys1295phe (accessed [today's date]).

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