Is PARP14 p.Val1270Ile (c.3808G>A) pathogenic?

PARP14 p.Val1270Ile (c.3808G>A) is classified Uncertain significance in PARP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-14). AlphaMissense: likely benign (0.1047); Very rare (popmax 0.00446%, eas).

How common is PARP14 p.Val1270Ile (c.3808G>A) in the general population?

PARP14 p.Val1270Ile (c.3808G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about PARP14 p.Val1270Ile (c.3808G>A)?

AlphaMissense predicts likely benign (score 0.1047) — an in-silico prediction, not a clinical call.

PARP14 p.Val1270Ile

c.3808G>A · rs1377728773 · VCV2624293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1047 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1047	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 47 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	23.0	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 0.00446% East Asian · 2/44,866 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000248% 4/1,612,798 alleles · very rare exomes 2/1,460,610 · genomes 2/152,188 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,433
European (non-Finnish)	0.00017%	589,480

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.Val1270Ile
Coding: c.3808G>A
MANE Select: NM_017554
dbSNP: rs1377728773
Type: single nucleotide variant
Location: chr3:122713910 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.00 · 47 PDB
Residue 1270: the macro 3 domain; an α-helix

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-val1270ile (accessed [today's date]).

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