Is TULP1 p.Val286fs (c.855dup) pathogenic?

TULP1 p.Val286fs (c.855dup) is classified Pathogenic/Likely pathogenic in TULP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-18). Very rare (popmax 0.0022%, sas); Associated with retinitis pigmentosa.

What condition is associated with TULP1 p.Val286fs (c.855dup)?

TULP1 p.Val286fs (c.855dup) is associated with retinitis pigmentosa, Leber congenital amaurosis (ClinVar).

How common is TULP1 p.Val286fs (c.855dup) in the general population?

TULP1 p.Val286fs (c.855dup) is very rare (popmax 0.0022%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TULP1 p.Val286fs

c.855dup · rs1554125752 · VCV505327

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

retinitis pigmentosa

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 10 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.13	GERP -1.5

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,056 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000806% 13/1,613,504 alleles · very rare exomes 13/1,461,212 · genomes 0/152,292 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,528
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000848%	117,988

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.Val286fs
Coding: c.855dup
MANE Select: NM_003322
dbSNP: rs1554125752
Type: Duplication
Location: chr6:35506146 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 286: the 'disordered' region

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Leber congenital amaurosis

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

TULP1 p.Val286Met Benign/Likely benign ★★ same residue
TULP1 c.1495+2dup Pathogenic ★ same condition
TULP1 p.Ile139fs Likely pathogenic ★ same condition
TULP1 p.Lys333fs Pathogenic ★ same condition
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg311Gln Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg311Trp Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg400Gln 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-val286fs (accessed [today's date]).

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