Is PARP14 p.Ile1605Val (c.4813A>G) pathogenic?

PARP14 p.Ile1605Val (c.4813A>G) is classified Uncertain significance in PARP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely benign (0.0741); Ultra-rare (popmax 0.0112%, nfe).

How common is PARP14 p.Ile1605Val (c.4813A>G) in the general population?

PARP14 p.Ile1605Val (c.4813A>G) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

What do computational predictors say about PARP14 p.Ile1605Val (c.4813A>G)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

PARP14 p.Ile1605Val

c.4813A>G · VCV3414236

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.88	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 -0.64	GERP -4.1
Regional constraint	o/e 0.83	unconstrained · MANE · 47 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	6.202	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 0.0112% European (non-Finnish) · 132/1,179,514 alleles

Filtering AF 0.00961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00843% 136/1,612,986 alleles · ultra-rare exomes 134/1,460,764 · genomes 2/152,222 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0112%	8,936
Remaining individualsnot grpmax-eligible	0.0048%	20,814
South Asian	0.0011%	90,762

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.Ile1605Val
Coding: c.4813A>G
MANE Select: NM_017554
Type: single nucleotide variant
Location: chr3:122720260 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.00 · 47 PDB
Residue 1605: the parp catalytic domain

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-ile1605val (accessed [today's date]).

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