Is TRPS1 p.Pro114= (c.342G>A) pathogenic?

TRPS1 p.Pro114= (c.342G>A) is classified Likely benign in TRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). Very rare (popmax 0.01%, amr); Associated with trichorhinophalangeal syndrome type I.

What condition is associated with TRPS1 p.Pro114= (c.342G>A)?

TRPS1 p.Pro114= (c.342G>A) is associated with trichorhinophalangeal syndrome type I (ClinVar).

How common is TRPS1 p.Pro114= (c.342G>A) in the general population?

TRPS1 p.Pro114= (c.342G>A) is very rare (popmax 0.01%, amr) (gnomAD).

TRPS1 p.Pro114=

c.342G>A · rs200131404 · VCV1641548

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Conditions

trichorhinophalangeal syndrome type I

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.1	GERP -5.5
Overall
CADD	6.757	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,016 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00421% 68/1,614,150 alleles · very rare exomes 59/1,461,890 · genomes 9/152,260 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,003
African / African-American	0.008%	12,506
European (non-Finnish)	0.00424%	23,601
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,253
East Asian	0.00223%	44,874

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: TRPS1
Protein: p.Pro114=
Coding: c.342G>A
MANE Select: NM_014112
dbSNP: rs200131404
Type: single nucleotide variant
Location: chr8:115619756 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12
Residue 114: 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.Pro114Leu Uncertain significance ★ ⚠ same residue
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

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-pro114 (accessed [today's date]).

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