Is PARP14 p.His875Asp (c.2623C>G) pathogenic?

PARP14 p.His875Asp (c.2623C>G) is classified Uncertain significance in PARP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.1523); Absent from gnomAD v4.1.

How common is PARP14 p.His875Asp (c.2623C>G) in the general population?

PARP14 p.His875Asp (c.2623C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PARP14 p.His875Asp (c.2623C>G)?

AlphaMissense predicts likely benign (score 0.1523) — an in-silico prediction, not a clinical call.

PARP14 p.His875Asp

c.2623C>G · VCV3304377

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1523 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1523	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -4.06	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 -0.57	GERP -2.2
Regional constraint	o/e 0.83	unconstrained · MANE · 47 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	17.44	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.

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: PARP14
Protein: p.His875Asp
Coding: c.2623C>G
MANE Select: NM_017554
Type: single nucleotide variant
Location: chr3:122701177 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.00 · 47 PDB
Residue 875: the macro 1 domain; a β-strand

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

Similar variants

PARP14 p.His875Asn Uncertain significance ★ ⚠ same residue
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

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-his875asp (accessed [today's date]).

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