Is TULP1 p.Pro242fs (c.725_728del) pathogenic?

TULP1 p.Pro242fs (c.725728del) is classified Pathogenic in TULP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-31). Very rare (popmax 0.000508%, nfe).

How common is TULP1 p.Pro242fs (c.725_728del) in the general population?

TULP1 p.Pro242fs (c.725_728del) is very rare (popmax 0.000508%, nfe) (gnomAD).

TULP1 p.Pro242fs

c.725_728del · rs771723580 · VCV198784

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000508%, 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 8 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -0.23, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,179,958 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,882 alleles · very rare exomes 2/1,461,790 · genomes 4/152,092 · 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.Pro242fs
Coding: c.725_728del
MANE Select: NM_003322
dbSNP: rs771723580
Type: Deletion
Location: chr6:35509303 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 242: the 'disordered' region

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

Similar variants

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.Pro282fs Pathogenic ★★ same type
TULP1 p.Ser210fs Pathogenic ★★ same type
TULP1 p.Phe528fs Uncertain significance ★★ same type
TULP1 c.1323+20_1323+34del Likely benign ★★ 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-pro242fs (accessed [today's date]).

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