Is TULP1 p.Pro282= (c.846G>A) pathogenic?

TULP1 p.Pro282= (c.846G>A) is classified Conflicting classifications of pathogenicity in TULP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0946%, afr); Associated with Leber congenital amaurosis 15.

What condition is associated with TULP1 p.Pro282= (c.846G>A)?

TULP1 p.Pro282= (c.846G>A) is associated with Leber congenital amaurosis 15, retinitis pigmentosa (ClinVar).

How common is TULP1 p.Pro282= (c.846G>A) in the general population?

TULP1 p.Pro282= (c.846G>A) is ultra-rare (popmax 0.0946%, afr) (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.Pro282=

c.846G>A · rs149980694 · VCV287340

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0946%, afr)

Conditions

Leber congenital amaurosis 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.4	GERP -3.9
Overall
CADD	0.382	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0946% African / African-American · 71/75,034 alleles

Filtering AF 0.0769% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0704%

Overall 0.00576% 93/1,613,516 alleles · ultra-rare exomes 48/1,461,242 · genomes 45/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0946%	1,057
European (non-Finnish)	0.00161%	62,098
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00157%	63,630
South Asian	0.0011%	91,066

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.Pro282=
Coding: c.846G>A
MANE Select: NM_003322
dbSNP: rs149980694
Type: single nucleotide variant
Location: chr6:35506156 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 282: 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

Also linked: retinitis pigmentosa

For Leber congenital amaurosis (Orphanet):

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

Similar variants

TULP1 p.Pro282Leu 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-pro282 (accessed [today's date]).

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