Is TRPS1 p.Ser489fs (c.1464_1474del) pathogenic?

TRPS1 p.Ser489fs (c.14641474del) is classified Likely pathogenic in TRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-22). Absent from gnomAD; Associated with trichorhinophalangeal syndrome type I.

What condition is associated with TRPS1 p.Ser489fs (c.1464_1474del)?

TRPS1 p.Ser489fs (c.1464_1474del) is associated with trichorhinophalangeal syndrome type I (ClinVar).

How common is TRPS1 p.Ser489fs (c.1464_1474del) in the general population?

TRPS1 p.Ser489fs (c.1464_1474del) is absent from gnomAD (gnomAD).

TRPS1 p.Ser489fs

c.1464_1474del · rs1817986949 · VCV972710

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 4 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 2.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRPS1
Protein: p.Ser489fs
Coding: c.1464_1474del
MANE Select: NM_014112
dbSNP: rs1817986949
Type: Deletion
Location: chr8:115604495 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12
Residue 489: the 'disordered' 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.Ser489= Likely benign ★ same residue
TRPS1 c.1919_2096+2929del Likely pathogenic ★ same condition
TRPS1 p.Ala131fs Pathogenic ★ same condition
TRPS1 p.Arg1220fs Pathogenic ★ same condition
TRPS1 p.Arg268fs Pathogenic ★ same condition
TRPS1 p.Arg944fs Pathogenic ★ same condition
TRPS1 p.Arg961fs Pathogenic ★ same condition
TRPS1 p.Asn199fs 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-ser489fs (accessed [today's date]).

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