Is TCAP p.Arg87Trp (c.259C>T) pathogenic?

TCAP p.Arg87Trp (c.259C>T) is classified Conflicting classifications of pathogenicity in TCAP (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.1757); Very rare (popmax 0.00503%, amr); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with TCAP p.Arg87Trp (c.259C>T)?

TCAP p.Arg87Trp (c.259C>T) is associated with familial hypertrophic cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy 25 (ClinVar).

How common is TCAP p.Arg87Trp (c.259C>T) in the general population?

TCAP p.Arg87Trp (c.259C>T) is very rare (popmax 0.00503%, amr) (gnomAD).

What do computational predictors say about TCAP p.Arg87Trp (c.259C>T)?

AlphaMissense predicts likely benign (score 0.1757) — an in-silico prediction, not a clinical call.

TCAP p.Arg87Trp

c.259C>T · rs777518512 · VCV202102

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00503%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

familial hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.1757	likely benign
REVEL	0.568	indeterminate
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 746 bp · p 0.44 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00503% Admixed American · 3/59,680 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00067%

Overall 0.000931% 15/1,610,498 alleles · very rare exomes 12/1,458,316 · genomes 3/152,182 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00678%	14,755
Admixed Americangrpmax	0.00503%	19,893
Remaining individualsnot grpmax-eligible	0.0016%	62,328
Finnishnot grpmax-eligible	0.0016%	62,482
South Asian	0.0011%	90,764
European (non-Finnish)	0.000594%	168,434

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TCAP
Protein: p.Arg87Trp
Coding: c.259C>T
MANE Select: NM_003673
dbSNP: rs777518512
Type: single nucleotide variant
Location: chr17:39665864 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 87: a UniProt-annotated variant site (found in a patient with dilated cardiomyopathy; uncertain significance)

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

Disease context

familial hypertrophic cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy hypertrophic cardiomyopathy 25

Similar variants

TCAP p.Arg87Gln Uncertain significance ★★ ⚠ same residue
TCAP p.Arg87= Likely benign ★★ same residue
TCAP p.Cys57Ter Pathogenic/Likely pathogenic ★★ same condition
TCAP p.Gln53Ter Pathogenic/Likely pathogenic ★★ same condition
TCAP p.Glu35Ter Pathogenic ★★ same condition
TCAP p.Trp22Ter Pathogenic/Likely pathogenic ★★ same condition
TCAP p.Trp25Ter Pathogenic/Likely pathogenic ★★ same condition
TCAP c.110+4A>G 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/tcap-p-arg87trp (accessed [today's date]).

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