Is TULP1 p.Arg400Pro (c.1199G>C) pathogenic?

TULP1 p.Arg400Pro (c.1199G>C) is classified Uncertain significance in TULP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-04). AlphaMissense: likely pathogenic (0.9896); Absent from gnomAD v4.1.

How common is TULP1 p.Arg400Pro (c.1199G>C) in the general population?

TULP1 p.Arg400Pro (c.1199G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TULP1 p.Arg400Pro (c.1199G>C)?

AlphaMissense predicts likely pathogenic (score 0.9896) — an in-silico prediction, not a clinical call.

TULP1 p.Arg400Pro

c.1199G>C · VCV4847480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9896 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9896	likely pathogenic · top 7% in TULP1
REVEL	0.961	strongly pathogenic-leaning
SaProt	LLR -13.68	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 7.6	GERP 1.9, 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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Arg400Pro
Coding: c.1199G>C
MANE Select: NM_003322
Type: single nucleotide variant
Location: chr6:35503762 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 400: a UniProt-annotated variant site (in lca15)

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

Similar variants

TULP1 p.Arg400Gln Pathogenic/Likely pathogenic ★★ same residue
TULP1 p.Arg400Trp Pathogenic/Likely pathogenic ★★ same residue
TULP1 c.1112+1G>A Likely pathogenic ★★ same type
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.718+2T>C Pathogenic ★★ same type
TULP1 c.99+1G>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.999+5G>C Pathogenic/Likely pathogenic ★★ same type

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-arg400pro (accessed [today's date]).

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