Is PARP14 p.Ala864= (c.2592C>T) pathogenic?

PARP14 p.Ala864= (c.2592C>T) is classified Benign in PARP14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 8.89%, afr) — too common for a highly-penetrant pathogenic allele.

PARP14 p.Ala864=

Q: How common is PARP14 p.Ala864= (c.2592C>T) in the general population?

PARP14 p.Ala864= (c.2592C>T) is common (popmax 8.89%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2592C>T · rs16833421 · VCV778107

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.89%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.2	GERP -3.5
Overall
CADD	2.873	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.89% African / African-American · 6,672/75,022 alleles

Filtering AF 8.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.64%

Overall 0.496% 8,009/1,613,894 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.89%	11
Admixed American	0.958%	104
Remaining individualsnot grpmax-eligible	0.695%	144
Middle Eastern	0.478%	209
European (non-Finnish)	0.0236%	4,229
South Asian	0.0209%	4,793
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Ala864=
Coding: c.2592C>T
MANE Select: NM_017554
dbSNP: rs16833421
Type: single nucleotide variant
Location: chr3:122701146 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.00 · 47 PDB
Residue 864: 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.Pro1200Leu Uncertain significance ★★ ⚠ same type
PARP14 p.Ala1513Val 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
PARP14 p.Ala385Ser 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-ala864 (accessed [today's date]).

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