Is TRPS1 p.Ala196Val (c.587C>T) pathogenic?

TRPS1 p.Ala196Val (c.587C>T) is classified Uncertain significance in TRPS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-20). AlphaMissense: likely benign (0.0917); Very rare (popmax 0.00288%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRPS1 p.Ala196Val (c.587C>T)?

TRPS1 p.Ala196Val (c.587C>T) is associated with Inborn genetic diseases, trichorhinophalangeal syndrome type I (ClinVar).

How common is TRPS1 p.Ala196Val (c.587C>T) in the general population?

TRPS1 p.Ala196Val (c.587C>T) is very rare (popmax 0.00288%, nfe) (gnomAD).

What do computational predictors say about TRPS1 p.Ala196Val (c.587C>T)?

AlphaMissense predicts likely benign (score 0.0917) — an in-silico prediction, not a clinical call.

TRPS1 p.Ala196Val

c.587C>T · rs1013920791 · VCV2933502

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0917	likely benign
REVEL	0.431	indeterminate
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2, 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 A183V vs ClinVar A196V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00288% European (non-Finnish) · 34/1,180,020 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00239% 35/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00288%	34,706
South Asian	0.0011%	91,080

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.Ala196Val
Coding: c.587C>T
MANE Select: NM_014112
dbSNP: rs1013920791
Type: single nucleotide variant
Location: chr8:115619511 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.12
Residue 196: 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

Also linked: trichorhinophalangeal syndrome type I

Similar variants

TRPS1 p.Ala196Thr 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
TRPS1 p.Arg696Ter 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-ala196val (accessed [today's date]).

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