Is TULP1 p.Arg34Ter (c.100C>T) pathogenic?

TULP1 p.Arg34Ter (c.100C>T) is classified Pathogenic in TULP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-07-19). Very rare (popmax 0.000281%, nfe); Associated with TULP1-related disorder.

What condition is associated with TULP1 p.Arg34Ter (c.100C>T)?

TULP1 p.Arg34Ter (c.100C>T) is associated with TULP1-related disorder, Leber congenital amaurosis 15 (ClinVar).

How common is TULP1 p.Arg34Ter (c.100C>T) in the general population?

TULP1 p.Arg34Ter (c.100C>T) is very rare (popmax 0.000281%, nfe) (gnomAD).

TULP1 p.Arg34Ter

c.100C>T · rs1331834680 · VCV867084

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000281%, nfe)

Conditions

TULP1-related disorder

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 3 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP -2.4, phastCons 0.18
Overall
CADD	35.0	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 0.000281% European (non-Finnish) · 3/1,068,020 alleles

Filtering AF 7.5e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.1e-05%

Overall 0.000216% 3/1,388,424 alleles · very rare exomes 2/1,236,378 · genomes 1/152,046 · joint denominator

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: TULP1
Protein: p.Arg34Ter
Coding: c.100C>T
MANE Select: NM_003322
dbSNP: rs1331834680
Type: single nucleotide variant
Location: chr6:35512270 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 34: the 'disordered' region

Full TULP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TULP1-related disorder

Also linked: Leber congenital amaurosis 15

Similar variants

TULP1 p.Arg34= Uncertain significance ★ same residue
TULP1 c.1112+1G>A Likely pathogenic ★★ same condition
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.718+2T>C Pathogenic ★★ same condition
TULP1 c.99+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.999+5G>C Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg311Gln Pathogenic/Likely 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/tulp1-p-arg34ter (accessed [today's date]).

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