Is PARP14 p.Gly255Val (c.764G>T) pathogenic?

PARP14 p.Gly255Val (c.764G>T) is classified Uncertain significance in PARP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-06). AlphaMissense: ambiguous (0.5239); Ultra-rare (popmax 0.02%, afr).

How common is PARP14 p.Gly255Val (c.764G>T) in the general population?

PARP14 p.Gly255Val (c.764G>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about PARP14 p.Gly255Val (c.764G>T)?

AlphaMissense predicts ambiguous (score 0.5239) — an in-silico prediction, not a clinical call.

PARP14 p.Gly255Val

c.764G>T · VCV3885718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5239 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Computational evidence

Protein change
AlphaMissense	0.5239	ambiguous
REVEL	0.639	indeterminate
SaProt	LLR -17.27	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 47 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	26.5	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 0.02% African / African-American · 15/74,848 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0099%

Overall 0.00124% 20/1,610,958 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,990
Admixed American	0.00501%	19,963
South Asian	0.0022%	45,417

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.Gly255Val
Coding: c.764G>T
MANE Select: NM_017554
Type: single nucleotide variant
Location: chr3:122695591 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.00 · 47 PDB

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-gly255val (accessed [today's date]).

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