Is TULP3 p.Arg24Ter (c.70C>T) pathogenic?

TULP3 p.Arg24Ter (c.70C>T) is classified Pathogenic in TULP3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-27). Very rare (popmax 0.0083%, nfe); Associated with hepatorenocardiac degenerative fibrosis.

What condition is associated with TULP3 p.Arg24Ter (c.70C>T)?

TULP3 p.Arg24Ter (c.70C>T) is associated with hepatorenocardiac degenerative fibrosis (ClinVar).

How common is TULP3 p.Arg24Ter (c.70C>T) in the general population?

TULP3 p.Arg24Ter (c.70C>T) is very rare (popmax 0.0083%, nfe) (gnomAD).

TULP3 p.Arg24Ter

c.70C>T · rs201665307 · VCV1687116

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0083%, nfe)

Conditions

hepatorenocardiac degenerative fibrosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.3, phastCons 1
Overall
CADD	37.0	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

Grpmax group 0.0083% European (non-Finnish) · 97/1,168,358 alleles

Filtering AF 0.00696% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0064%

Overall 0.0068% 107/1,573,348 alleles · very rare exomes 97/1,422,046 · genomes 10/151,302 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0083%	12,045
Admixed American	0.00636%	15,721
African / African-American	0.00423%	23,643
South Asian	0.00356%	28,095
Remaining individualsnot grpmax-eligible	0.00165%	60,702

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: TULP3
Protein: p.Arg24Ter
Coding: c.70C>T
MANE Select: NM_003324
dbSNP: rs201665307
Type: single nucleotide variant
Location: chr12:2909557 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.51 · 1 PDB
Residue 24: the 'required for association with the ift complex a (ift-a)' region; a UniProt-annotated variant site (in hrcdf)

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.809+2T>C 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.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-p-arg24ter (accessed [today's date]).

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