Is TULP1 p.Thr484Pro (c.1450A>C) pathogenic?

TULP1 p.Thr484Pro (c.1450A>C) is classified Likely pathogenic in TULP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-01). AlphaMissense: likely pathogenic (0.9272); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with TULP1 p.Thr484Pro (c.1450A>C)?

TULP1 p.Thr484Pro (c.1450A>C) is associated with inherited retinal dystrophy (ClinVar).

How common is TULP1 p.Thr484Pro (c.1450A>C) in the general population?

TULP1 p.Thr484Pro (c.1450A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TULP1 p.Thr484Pro (c.1450A>C)?

AlphaMissense predicts likely pathogenic (score 0.9272) — an in-silico prediction, not a clinical call.

TULP1 p.Thr484Pro

c.1450A>C · VCV3248831

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9272 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9272	likely pathogenic ✓ concordant with ClinVar
REVEL	0.97	strongly pathogenic-leaning
SaProt	LLR -14.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,948 bp · p 0.64 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TULP1
Protein: p.Thr484Pro
Coding: c.1450A>C
MANE Select: NM_003322
Type: single nucleotide variant
Location: chr6:35500026 (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

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TULP1 p.Thr484Ile Uncertain significance ★ ⚠ same residue
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.718+2T>C Pathogenic ★★ same condition
TULP1 p.Arg361Ter Pathogenic ★★ same condition
TULP1 p.Arg400Trp Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg419Trp Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg440Ter Pathogenic ★★ same condition
TULP1 p.Asn349Lys 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-thr484pro (accessed [today's date]).

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