Is TRPS1 p.Ser799fs (c.2396dup) pathogenic?

TRPS1 p.Ser799fs (c.2396dup) is classified Likely pathogenic in TRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). Associated with trichorhinophalangeal syndrome type I.

What condition is associated with TRPS1 p.Ser799fs (c.2396dup)?

TRPS1 p.Ser799fs (c.2396dup) is associated with trichorhinophalangeal syndrome type I (ClinVar).

TRPS1 p.Ser799fs

c.2396dup · VCV4073596

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

trichorhinophalangeal syndrome type I

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.7	GERP -5.6

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

Variant & gene context

Gene: TRPS1
Protein: p.Ser799fs
Coding: c.2396dup
MANE Select: NM_014112
Type: Duplication
Location: chr8:115587304 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12
Residue 799: the 'mediates interaction with gli3' region

Full TRPS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

trichorhinophalangeal syndrome type I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRPS1 p.Ser799Arg Uncertain significance ★ ⚠ same residue
TRPS1 p.Asn393Ter Pathogenic ★★ same condition
TRPS1 p.Asn1289fs Uncertain significance ★★ same condition
TRPS1 c.-9dup Benign ★★ same condition
TRPS1 p.Ala932fs Pathogenic ★ same condition
TRPS1 p.Asn19fs Pathogenic ★ same condition
TRPS1 p.Asn967fs Pathogenic ★ same condition
TRPS1 p.Gln285fs 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/trps1-p-ser799fs (accessed [today's date]).

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