Is TRPS1 p.Ser524Phe (c.1571C>T) pathogenic?

TRPS1 p.Ser524Phe (c.1571C>T) is classified Uncertain significance in TRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-11). AlphaMissense: likely benign (0.1247); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRPS1 p.Ser524Phe (c.1571C>T)?

TRPS1 p.Ser524Phe (c.1571C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRPS1 p.Ser524Phe (c.1571C>T) in the general population?

TRPS1 p.Ser524Phe (c.1571C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRPS1 p.Ser524Phe (c.1571C>T)?

AlphaMissense predicts likely benign (score 0.1247) — an in-silico prediction, not a clinical call.

TRPS1 p.Ser524Phe

c.1571C>T · rs1817983119 · VCV2306720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1247 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1247	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -8.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 37 kb · p 0.11 · regional, not allelic
Overall
CADD	24.0	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 S511F vs ClinVar S524F) — 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.Ser524Phe
Coding: c.1571C>T
MANE Select: NM_014112
dbSNP: rs1817983119
Type: single nucleotide variant
Location: chr8:115604398 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12
Residue 511 UniProt numbering: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRPS1 p.Ser524= Likely benign ★ same residue
TRPS1 p.Arg696Ter Pathogenic ★★ same condition
TRPS1 p.Ala196Val Uncertain significance ★★ ⚠ same condition
TRPS1 p.Ala848Thr Uncertain significance ★★ ⚠ same condition
TRPS1 p.Arg1125Gln Uncertain significance ★★ ⚠ same condition
TRPS1 p.Asn738Ser Uncertain significance ★★ ⚠ same condition
TRPS1 p.Cys704Ser Uncertain significance ★★ ⚠ same condition
TRPS1 p.Gln1020His Uncertain significance ★★ ⚠ 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-ser524phe (accessed [today's date]).

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