Is TRPS1 p.Val1035= (c.3105C>T) pathogenic?

TRPS1 p.Val1035= (c.3105C>T) is classified Likely benign in TRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). Ultra-rare (popmax 0.0484%, amr); Associated with trichorhinophalangeal syndrome type I.

What condition is associated with TRPS1 p.Val1035= (c.3105C>T)?

TRPS1 p.Val1035= (c.3105C>T) is associated with trichorhinophalangeal syndrome type I (ClinVar).

How common is TRPS1 p.Val1035= (c.3105C>T) in the general population?

TRPS1 p.Val1035= (c.3105C>T) is ultra-rare (popmax 0.0484%, amr) (gnomAD).

TRPS1 p.Val1035=

c.3105C>T · rs753629655 · VCV1595573

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0484%, 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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 10	GERP 1.7, phastCons 1
Overall
CADD	9.212	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0484% Admixed American · 29/59,952 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.00186% 30/1,613,880 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0484%	2,067
European (non-Finnish)	8.47e-05%	1,179,958

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.Val1035=
Coding: c.3105C>T
MANE Select: NM_014112
dbSNP: rs753629655
Type: single nucleotide variant
Location: chr8:115414803 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12
Residue 1035: the 'mediates interaction with rnf4' 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 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-val1035 (accessed [today's date]).

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