Is TULP1 p.Leu477Val (c.1429C>G) pathogenic?

TULP1 p.Leu477Val (c.1429C>G) is classified Conflicting classifications of pathogenicity in TULP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-09-01). AlphaMissense: likely pathogenic (0.9364); Absent from gnomAD v4.1; Associated with TULP1-related disorder.

What condition is associated with TULP1 p.Leu477Val (c.1429C>G)?

TULP1 p.Leu477Val (c.1429C>G) is associated with TULP1-related disorder (ClinVar).

How common is TULP1 p.Leu477Val (c.1429C>G) in the general population?

TULP1 p.Leu477Val (c.1429C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TULP1 p.Leu477Val (c.1429C>G)?

AlphaMissense predicts likely pathogenic (score 0.9364) — an in-silico prediction, not a clinical call.

TULP1 p.Leu477Val

c.1429C>G · rs1768799281 · VCV1037300

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9364 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TULP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9364	likely pathogenic
REVEL	0.961	strongly pathogenic-leaning
SaProt	LLR -14.03	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,948 bp · p 0.64 · regional, not allelic
Overall
CADD	28.5	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.Leu477Val
Coding: c.1429C>G
MANE Select: NM_003322
dbSNP: rs1768799281
Type: single nucleotide variant
Location: chr6:35500047 (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

TULP1-related disorder

Similar variants

TULP1 p.Leu477= Likely benign ★ same residue
TULP1 c.1112+1G>A Likely pathogenic ★★ same condition
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.718+2T>C Pathogenic ★★ same condition
TULP1 c.999+5G>C Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg342Ter Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg34Ter 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-leu477val (accessed [today's date]).

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