Is TCAP p.Arg63Cys (c.187C>T) pathogenic?

TCAP p.Arg63Cys (c.187C>T) is classified Uncertain significance in TCAP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.105); Ultra-rare (popmax 0.0455%, amr); Associated with Cardiovascular phenotype.

What condition is associated with TCAP p.Arg63Cys (c.187C>T)?

TCAP p.Arg63Cys (c.187C>T) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy 25, familial hypertrophic cardiomyopathy (ClinVar).

How common is TCAP p.Arg63Cys (c.187C>T) in the general population?

TCAP p.Arg63Cys (c.187C>T) is ultra-rare (popmax 0.0455%, amr) (gnomAD).

What do computational predictors say about TCAP p.Arg63Cys (c.187C>T)?

AlphaMissense predicts likely benign (score 0.105) — an in-silico prediction, not a clinical call.

TCAP p.Arg63Cys

c.187C>T · rs758048577 · VCV464945

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.105 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0455%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.105	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -6.89	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 0.81	GERP -1.8, phastCons 0.24
Regional constraint	o/e 0.95	unconstrained · MANE · 746 bp · p 0.44 · regional, not allelic
Overall
CADD	16.14	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0455% Admixed American · 27/59,358 alleles

Filtering AF 0.032% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0276%

Overall 0.00305% 49/1,607,540 alleles · ultra-rare exomes 24/1,455,356 · genomes 25/152,184 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0455%	2,198
Middle Eastern	0.0166%	6,026
Remaining individualsnot grpmax-eligible	0.00482%	20,749
South Asian	0.00222%	45,082
African / African-American	0.00134%	74,854
European (non-Finnish)	0.00127%	78,488

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.Arg63Cys
Coding: c.187C>T
MANE Select: NM_003673
dbSNP: rs758048577
Type: single nucleotide variant
Location: chr17:39665792 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 25 familial hypertrophic cardiomyopathy

Similar variants

TCAP p.Arg63His Uncertain significance ★★ ⚠ same residue
TCAP p.Arg63= 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-arg63cys (accessed [today's date]).

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