Is TULP3 c.809+2T>C pathogenic?

TULP3 c.809+2T>C is classified Pathogenic in TULP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). Absent from gnomAD v4.1; Associated with hepatorenocardiac degenerative fibrosis.

What condition is associated with TULP3 c.809+2T>C?

TULP3 c.809+2T>C is associated with hepatorenocardiac degenerative fibrosis (ClinVar).

How common is TULP3 c.809+2T>C in the general population?

TULP3 c.809+2T>C is absent from gnomAD v4.1 (gnomAD).

TULP3 c.809+2T>C

rs2536387265 · VCV2444270

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hepatorenocardiac degenerative fibrosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.98	donor loss · deltas
Pangolin	Δ0.86	loss · gain 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5	GERP 0.42, phastCons 1
Non-coding constraint	Z 1.01	1 kb window · o/e 0.93 · regional · uncalibrated
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: TULP3
Coding: c.809+2T>C
MANE Select: NM_003324
dbSNP: rs2536387265
Type: single nucleotide variant
Location: chr12:2933532 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.51 · 1 PDB

Full TULP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hepatorenocardiac degenerative fibrosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TULP3 c.492+1G>A Likely pathogenic ★ same condition
TULP3 c.810-1G>C Likely pathogenic ★ same condition
TULP3 p.Arg382Gln Uncertain significance ★ ⚠ same condition
TULP3 p.Cys204Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
TULP3 p.Leu235Pro Uncertain significance ★ ⚠ same condition
TULP3 c.1023+1G>A Pathogenic same condition
TULP3 p.Arg24Ter Pathogenic same condition
TULP3 p.Arg382Trp Pathogenic same condition

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/tulp3-c-809-plus-2t-c (accessed [today's date]).

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