Is PARP14 p.Ala799Asp (c.2396C>A) pathogenic?

PARP14 p.Ala799Asp (c.2396C>A) is classified Uncertain significance in PARP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely benign (0.2008); Ultra-rare (popmax 0.0116%, nfe).

How common is PARP14 p.Ala799Asp (c.2396C>A) in the general population?

PARP14 p.Ala799Asp (c.2396C>A) is ultra-rare (popmax 0.0116%, nfe) (gnomAD).

What do computational predictors say about PARP14 p.Ala799Asp (c.2396C>A)?

AlphaMissense predicts likely benign (score 0.2008) — an in-silico prediction, not a clinical call.

PARP14 p.Ala799Asp

c.2396C>A · rs199869051 · VCV2356723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2008 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2008	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -6.77	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 0.14	GERP -0.69, phastCons 0.003
Regional constraint	o/e 0.83	unconstrained · MANE · 47 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	10.98	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

Grpmax group 0.0116% European (non-Finnish) · 137/1,179,882 alleles

Filtering AF 0.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00939%

Overall 0.00905% 146/1,614,004 alleles · ultra-rare exomes 143/1,461,674 · genomes 3/152,330 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0116%	8,612
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.00666%	15,006

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.Ala799Asp
Coding: c.2396C>A
MANE Select: NM_017554
dbSNP: rs199869051
Type: single nucleotide variant
Location: chr3:122700950 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.00 · 47 PDB
Residue 799: 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.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-ala799asp (accessed [today's date]).

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