Is PARP14 p.Pro1200Leu (c.3599C>T) pathogenic?

PARP14 p.Pro1200Leu (c.3599C>T) is classified Uncertain significance in PARP14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-16). AlphaMissense: likely benign (0.0964); Ultra-rare (popmax 0.027%, sas).

How common is PARP14 p.Pro1200Leu (c.3599C>T) in the general population?

PARP14 p.Pro1200Leu (c.3599C>T) is ultra-rare (popmax 0.027%, sas) (gnomAD).

What do computational predictors say about PARP14 p.Pro1200Leu (c.3599C>T)?

AlphaMissense predicts likely benign (score 0.0964) — an in-silico prediction, not a clinical call.

PARP14 p.Pro1200Leu

c.3599C>T · rs745695997 · VCV2307601

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0964 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0964	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -7.07	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 1.2	GERP 2, phastCons 0.001
Regional constraint	o/e 0.83	unconstrained · MANE · 47 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	14.09	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 0.027% South Asian · 23/85,328 alleles

Filtering AF 0.0184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0156%

Overall 0.00249% 39/1,567,016 alleles · ultra-rare exomes 38/1,415,012 · genomes 1/152,004 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.027%	3,710
East Asian	0.00691%	14,476
Remaining individualsnot grpmax-eligible	0.00328%	30,444
Admixed American	0.00185%	54,200
European (non-Finnish)	0.000868%	115,202

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.Pro1200Leu
Coding: c.3599C>T
MANE Select: NM_017554
dbSNP: rs745695997
Type: single nucleotide variant
Location: chr3:122708248 (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.Pro1200Ala Uncertain significance ★ ⚠ same residue
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-pro1200leu (accessed [today's date]).

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