Is TRPS1 p.Arg900= (c.2700G>C) pathogenic?

TRPS1 p.Arg900= (c.2700G>C) is classified Uncertain significance in TRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-23). Absent from gnomAD v4.1; Associated with Trichorhinophalangeal syndrome, type III.

What condition is associated with TRPS1 p.Arg900= (c.2700G>C)?

TRPS1 p.Arg900= (c.2700G>C) is associated with Trichorhinophalangeal syndrome, type III, trichorhinophalangeal syndrome type I (ClinVar).

How common is TRPS1 p.Arg900= (c.2700G>C) in the general population?

TRPS1 p.Arg900= (c.2700G>C) is absent from gnomAD v4.1 (gnomAD).

TRPS1 p.Arg900=

c.2700G>C · rs2130443039 · VCV1505084

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Trichorhinophalangeal syndrome, type III

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.87	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.57	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

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: TRPS1
Protein: p.Arg900=
Coding: c.2700G>C
MANE Select: NM_014112
dbSNP: rs2130443039
Type: single nucleotide variant
Location: chr8:115587001 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12

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

Disease context

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

Also linked: trichorhinophalangeal syndrome type I

Similar variants

TRPS1 c.2097-2A>C Pathogenic/Likely pathogenic ★★ same condition
TRPS1 p.Ala932Thr Pathogenic/Likely pathogenic ★★ same condition
TRPS1 p.Ala932Val Pathogenic ★★ same condition
TRPS1 p.Arg257Ter Pathogenic ★★ same condition
TRPS1 p.Arg544Ter Pathogenic ★★ same condition
TRPS1 p.Arg624Ter Pathogenic ★★ same condition
TRPS1 p.Arg696Ter Pathogenic ★★ same condition
TRPS1 p.Arg921Gln 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-arg900 (accessed [today's date]).

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