Is TRPS1 p.Ser606Phe (c.1817C>T) pathogenic?

TRPS1 p.Ser606Phe (c.1817C>T) is classified Likely pathogenic in TRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-05). AlphaMissense: likely pathogenic (0.7475); Absent from gnomAD v4.1; Associated with trichorhinophalangeal syndrome type I.

What condition is associated with TRPS1 p.Ser606Phe (c.1817C>T)?

TRPS1 p.Ser606Phe (c.1817C>T) is associated with trichorhinophalangeal syndrome type I (ClinVar).

How common is TRPS1 p.Ser606Phe (c.1817C>T) in the general population?

TRPS1 p.Ser606Phe (c.1817C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRPS1 p.Ser606Phe (c.1817C>T)?

AlphaMissense predicts likely pathogenic (score 0.7475) — an in-silico prediction, not a clinical call.

TRPS1 p.Ser606Phe

c.1817C>T · rs1817974591 · VCV981461

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7475 · 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	0.7475	likely pathogenic ✓ concordant with ClinVar
REVEL	0.347	indeterminate
SaProt	LLR -8.09	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 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 37 kb · p 0.11 · regional, not allelic
Overall
CADD	26.9	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 S593F vs ClinVar S606F) — 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.Ser606Phe
Coding: c.1817C>T
MANE Select: NM_014112
dbSNP: rs1817974591
Type: single nucleotide variant
Location: chr8:115604152 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12

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-ser606phe (accessed [today's date]).

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