Is TULP1 p.Arg419fs (c.1255del) pathogenic?

TULP1 p.Arg419fs (c.1255del) is classified Pathogenic/Likely pathogenic in TULP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-03). Very rare (popmax 0.00516%, amr); Associated with TULP1-related disorder.

What condition is associated with TULP1 p.Arg419fs (c.1255del)?

TULP1 p.Arg419fs (c.1255del) is associated with TULP1-related disorder, retinitis pigmentosa 14, Leber congenital amaurosis 15 (ClinVar).

How common is TULP1 p.Arg419fs (c.1255del) in the general population?

TULP1 p.Arg419fs (c.1255del) is very rare (popmax 0.00516%, amr) (gnomAD).

TULP1 p.Arg419fs

c.1255del · rs1387418594 · VCV1028595

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00516%, amr)

Conditions

TULP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Overall
CADD	29.0	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 0.00516% Admixed American · 3/58,102 alleles

Filtering AF 0.00137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00068%

Overall 0.000188% 3/1,599,176 alleles · very rare exomes 2/1,446,974 · genomes 1/152,202 · 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.Arg419fs
Coding: c.1255del
MANE Select: NM_003322
dbSNP: rs1387418594
Type: Deletion
Location: chr6:35503627 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB

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

Disease context

TULP1-related disorder

Also linked: retinitis pigmentosa 14 Leber congenital amaurosis 15

Similar variants

TULP1 p.Arg419Trp Pathogenic/Likely pathogenic ★★ same residue
TULP1 p.Arg419Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TULP1 p.Gln485fs Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Leu504fs Pathogenic ★★ same condition
TULP1 p.Lys274fs Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Ser210fs Pathogenic ★★ same condition
TULP1 p.Arg419= Likely benign ★★ same residue
TULP1 p.Glu104fs 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-arg419fs (accessed [today's date]).

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