Is TIPARP p.Arg396Lys (c.1187G>A) pathogenic?

TIPARP p.Arg396Lys (c.1187G>A) is classified Uncertain significance in TIPARP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-12). AlphaMissense: likely benign (0.3399); Absent from gnomAD v4.1.

How common is TIPARP p.Arg396Lys (c.1187G>A) in the general population?

TIPARP p.Arg396Lys (c.1187G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TIPARP p.Arg396Lys (c.1187G>A)?

AlphaMissense predicts likely benign (score 0.3399) — an in-silico prediction, not a clinical call.

TIPARP p.Arg396Lys

c.1187G>A · rs2473565755 · VCV2559468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3399 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3399	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -5.99	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 12	phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 26 kb · p 0.0029 · regional, not allelic
Overall
CADD	23.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TIPARP
Protein: p.Arg396Lys
Coding: c.1187G>A
MANE Select: NM_015508
dbSNP: rs2473565755
Type: single nucleotide variant
Location: chr3:156695965 (GRCh38)
Gene constraint: LOEUF 0.346 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.00
Residue 396: the wwe domain

Full TIPARP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TIPARP p.Arg523= Benign ★★ same type
TIPARP p.Ala124Val Uncertain significance ★ ⚠ same type
TIPARP p.Arg133Leu Uncertain significance ★ ⚠ same type
TIPARP p.Arg272Gly Uncertain significance ★ ⚠ same type
TIPARP p.Arg28Lys Uncertain significance ★ ⚠ same type
TIPARP p.Arg366Gln Uncertain significance ★ ⚠ same type
TIPARP p.Arg374Trp Uncertain significance ★ ⚠ same type
TIPARP p.Arg406His 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/tiparp-p-arg396lys (accessed [today's date]).

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