Is TULP1 p.Pro175fs (c.524del) pathogenic?

TULP1 p.Pro175fs (c.524del) is classified Pathogenic in TULP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-05). Very rare (popmax 8.47e-05%, nfe).

How common is TULP1 p.Pro175fs (c.524del) in the general population?

TULP1 p.Pro175fs (c.524del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

TULP1 p.Pro175fs

c.524del · rs1327062642 · VCV2826305

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.39	GERP -3.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,942 alleles

Overall 6.2e-05% 1/1,613,670 alleles · very rare exomes 1/1,461,712 · genomes 0/151,958 · joint denominator

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.Pro175fs
Coding: c.524del
MANE Select: NM_003322
dbSNP: rs1327062642
Type: Deletion
Location: chr6:35509904 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 175: the 'disordered' region

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

Similar variants

TULP1 p.Pro175Ala Uncertain significance ★★ ⚠ same residue
TULP1 p.Pro175Thr Uncertain significance ★ ⚠ same residue
TULP1 p.Pro175= Likely benign ★ same residue
TULP1 p.Arg419fs Pathogenic/Likely pathogenic ★★ same type
TULP1 p.Gln485fs Pathogenic/Likely pathogenic ★★ same type
TULP1 p.Leu504fs Pathogenic ★★ same type
TULP1 p.Lys274fs Pathogenic/Likely pathogenic ★★ same type
TULP1 p.Pro242fs 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-pro175fs (accessed [today's date]).

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