Is TULP1 p.Ala276= (c.828G>A) pathogenic?

TULP1 p.Ala276= (c.828G>A) is classified Uncertain significance in TULP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-04-09). Very rare (popmax 0.000429%, nfe); Associated with retinitis pigmentosa 14.

What condition is associated with TULP1 p.Ala276= (c.828G>A)?

TULP1 p.Ala276= (c.828G>A) is associated with retinitis pigmentosa 14 (ClinVar).

How common is TULP1 p.Ala276= (c.828G>A) in the general population?

TULP1 p.Ala276= (c.828G>A) is very rare (popmax 0.000429%, 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.Ala276=

c.828G>A · rs929294496 · VCV968080

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000429%, nfe)

Conditions

retinitis pigmentosa 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.37	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.26	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.41	GERP 0.59, phastCons 0.69
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000429% European (non-Finnish) · 5/1,164,402 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000442% 7/1,582,296 alleles · very rare exomes 6/1,430,120 · genomes 1/152,176 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0069%	14,492
European (non-Finnish)grpmax	0.000429%	232,880

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala276=
Coding: c.828G>A
MANE Select: NM_003322
dbSNP: rs929294496
Type: single nucleotide variant
Location: chr6:35506274 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 276: the 'disordered' region

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

Disease context

retinitis pigmentosa 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

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

Similar variants

TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.718+2T>C 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.Arg361Ter 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-ala276 (accessed [today's date]).

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