Is TULP1 p.Cys53Ter (c.159C>A) pathogenic?

TULP1 p.Cys53Ter (c.159C>A) is classified Likely pathogenic in TULP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-20). No allele count reported in gnomAD v4.1 (AN 1,364,886); Associated with Leber congenital amaurosis 15.

What condition is associated with TULP1 p.Cys53Ter (c.159C>A)?

TULP1 p.Cys53Ter (c.159C>A) is associated with Leber congenital amaurosis 15 (ClinVar).

How common is TULP1 p.Cys53Ter (c.159C>A) in the general population?

TULP1 p.Cys53Ter (c.159C>A) is no allele count reported in gnomAD v4.1 (AN 1,364,886) (gnomAD).

How is Leber congenital amaurosis inherited?

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

TULP1 p.Cys53Ter

c.159C>A · VCV3341376

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,364,886)

Conditions

Leber congenital amaurosis 15

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.055	GERP -1.2, phastCons 0.003
Overall
CADD	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,364,886). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TULP1
Protein: p.Cys53Ter
Coding: c.159C>A
MANE Select: NM_003322
Type: single nucleotide variant
Location: chr6:35512211 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 53: the 'disordered' region

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

Disease context

Leber congenital amaurosis 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

TULP1 p.Cys53Arg Uncertain significance ★ ⚠ same residue
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.99+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg311Gln Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg311Trp Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg342Ter Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg34Ter 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-cys53ter (accessed [today's date]).

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