Is TRPS1 p.Ser388= (c.1164A>G) pathogenic?

TRPS1 p.Ser388= (c.1164A>G) is classified Benign in TRPS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-18). Rare (popmax 0.212%, afr); Associated with trichorhinophalangeal syndrome type I.

What condition is associated with TRPS1 p.Ser388= (c.1164A>G)?

TRPS1 p.Ser388= (c.1164A>G) is associated with trichorhinophalangeal syndrome type I (ClinVar).

How common is TRPS1 p.Ser388= (c.1164A>G) in the general population?

TRPS1 p.Ser388= (c.1164A>G) is rare (popmax 0.212%, afr) (gnomAD).

TRPS1 p.Ser388=

c.1164A>G · rs138244006 · VCV766855

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.212%, afr)

Conditions

trichorhinophalangeal syndrome type I

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.4	GERP -5.4
Overall
CADD	0.576	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.212% African / African-American · 159/75,056 alleles

Filtering AF 0.185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.175%

Overall 0.0103% 166/1,614,098 alleles · rare exomes 83/1,461,776 · genomes 83/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.212%	472
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Admixed American	0.005%	19,997

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.Ser388=
Coding: c.1164A>G
MANE Select: NM_014112
dbSNP: rs138244006
Type: single nucleotide variant
Location: chr8:115604805 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12
Residue 388: the 'disordered' 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 p.Ser388Ter Pathogenic ★ same residue
TRPS1 p.Ser388Ala Uncertain significance ★ ⚠ same residue
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

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-ser388 (accessed [today's date]).

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