Is TULP1 p.Pro521= (c.1563G>A) pathogenic?

TULP1 p.Pro521= (c.1563G>A) is classified Conflicting classifications of pathogenicity in TULP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-07). Very rare (popmax 0.00178%, nfe); Associated with retinitis pigmentosa.

What condition is associated with TULP1 p.Pro521= (c.1563G>A)?

TULP1 p.Pro521= (c.1563G>A) is associated with retinitis pigmentosa, Leber congenital amaurosis 15 (ClinVar).

How common is TULP1 p.Pro521= (c.1563G>A) in the general population?

TULP1 p.Pro521= (c.1563G>A) is very rare (popmax 0.00178%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

TULP1 p.Pro521=

c.1563G>A · rs1031077618 · VCV906794

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.096	GERP -4.2, phastCons 0.92
Overall
CADD	19.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,179,990 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,613,678 alleles · very rare exomes 17/1,461,452 · genomes 4/152,226 · 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.Pro521=
Coding: c.1563G>A
MANE Select: NM_003322
dbSNP: rs1031077618
Type: single nucleotide variant
Location: chr6:35498393 (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

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

Also linked: Leber congenital amaurosis 15

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.Pro521Leu Likely pathogenic ★ same residue
TULP1 p.Pro521Ser Likely pathogenic ★ same residue
TULP1 p.Pro521Thr Pathogenic ★ 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

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-pro521 (accessed [today's date]).

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