Is TRPS1 p.Arg1007Lys (c.3020G>A) pathogenic?

TRPS1 p.Arg1007Lys (c.3020G>A) is classified Uncertain significance in TRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-07). AlphaMissense: likely benign (0.1044); Very rare (popmax 0.00167%, amr); Associated with Trichorhinophalangeal syndrome, type III.

What condition is associated with TRPS1 p.Arg1007Lys (c.3020G>A)?

TRPS1 p.Arg1007Lys (c.3020G>A) is associated with Trichorhinophalangeal syndrome, type III, trichorhinophalangeal syndrome type I (ClinVar).

How common is TRPS1 p.Arg1007Lys (c.3020G>A) in the general population?

TRPS1 p.Arg1007Lys (c.3020G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about TRPS1 p.Arg1007Lys (c.3020G>A)?

AlphaMissense predicts likely benign (score 0.1044) — an in-silico prediction, not a clinical call.

TRPS1 p.Arg1007Lys

c.3020G>A · rs1351514084 · VCV2953368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1044 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Trichorhinophalangeal syndrome, type III

Computational evidence

Protein change
AlphaMissense	0.1044	likely benign
REVEL	0.515	indeterminate
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 980 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R994K vs ClinVar R1007K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,780 alleles

Overall 6.2e-05% 1/1,612,246 alleles · very rare exomes 1/1,460,048 · genomes 0/152,198 · joint denominator

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.Arg1007Lys
Coding: c.3020G>A
MANE Select: NM_014112
dbSNP: rs1351514084
Type: single nucleotide variant
Location: chr8:115414888 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12
Residue 994 UniProt numbering: the 'disordered' region; 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 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-arg1007lys (accessed [today's date]).

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