Is TRPS1 p.Phe1117Ser (c.3350T>C) pathogenic?

TRPS1 p.Phe1117Ser (c.3350T>C) is classified Uncertain significance in TRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-14). AlphaMissense: likely pathogenic (0.9322); Absent from gnomAD v4.1; Associated with trichorhinophalangeal syndrome type I.

What condition is associated with TRPS1 p.Phe1117Ser (c.3350T>C)?

TRPS1 p.Phe1117Ser (c.3350T>C) is associated with trichorhinophalangeal syndrome type I (ClinVar).

How common is TRPS1 p.Phe1117Ser (c.3350T>C) in the general population?

TRPS1 p.Phe1117Ser (c.3350T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRPS1 p.Phe1117Ser (c.3350T>C)?

AlphaMissense predicts likely pathogenic (score 0.9322) — an in-silico prediction, not a clinical call.

TRPS1 p.Phe1117Ser

c.3350T>C · rs1812867470 · VCV1027825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9322 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

trichorhinophalangeal syndrome type I

Computational evidence

Protein change
AlphaMissense	0.9322	likely pathogenic
REVEL	0.587	indeterminate
SaProt	LLR -6.27	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 980 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F1104S vs ClinVar F1117S) — verify the residue.

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.Phe1117Ser
Coding: c.3350T>C
MANE Select: NM_014112
dbSNP: rs1812867470
Type: single nucleotide variant
Location: chr8:115414558 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12
Residue 1117: 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-phe1117ser (accessed [today's date]).

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