Is TULP1 p.Arg482Trp (c.1444C>T) pathogenic?

TULP1 p.Arg482Trp (c.1444C>T) is classified Conflicting classifications of pathogenicity in TULP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-07-31). AlphaMissense: likely pathogenic (0.9668); Very rare (popmax 0.004%, afr); Associated with TULP1-related disorder.

What condition is associated with TULP1 p.Arg482Trp (c.1444C>T)?

TULP1 p.Arg482Trp (c.1444C>T) is associated with TULP1-related disorder, retinitis pigmentosa 14, Leber congenital amaurosis (ClinVar).

How common is TULP1 p.Arg482Trp (c.1444C>T) in the general population?

TULP1 p.Arg482Trp (c.1444C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about TULP1 p.Arg482Trp (c.1444C>T)?

AlphaMissense predicts likely pathogenic (score 0.9668) — an in-silico prediction, not a clinical call.

TULP1 p.Arg482Trp

c.1444C>T · rs121909077 · VCV7363

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9668 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TULP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9668	likely pathogenic
REVEL	0.966	strongly pathogenic-leaning
SaProt	LLR -14.98	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,948 bp · p 0.64 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.004% African / African-American · 3/74,918 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00198% 32/1,614,048 alleles · very rare exomes 30/1,461,868 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00937%	10,670
African / African-Americangrpmax	0.004%	24,973
South Asian	0.00329%	30,360
European (non-Finnish)	0.00169%	59,002

Finnish 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.Arg482Trp
Coding: c.1444C>T
MANE Select: NM_003322
dbSNP: rs121909077
Type: single nucleotide variant
Location: chr6:35500032 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 482: a UniProt-annotated variant site (in rp14)

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

Disease context

TULP1-related disorder

Also linked: retinitis pigmentosa 14 Leber congenital amaurosis

Similar variants

TULP1 p.Arg482Gln Pathogenic ★★ same residue
TULP1 p.Arg482Leu Likely pathogenic ★ same residue
TULP1 c.1112+1G>A Likely pathogenic ★★ same condition
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 c.999+5G>C 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-arg482trp (accessed [today's date]).

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