Is TCAP p.Cys8= (c.24C>T) pathogenic?

TCAP p.Cys8= (c.24C>T) is classified Likely benign in TCAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.011%, sas); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with TCAP p.Cys8= (c.24C>T)?

TCAP p.Cys8= (c.24C>T) is associated with familial hypertrophic cardiomyopathy, hypertrophic cardiomyopathy 25 (ClinVar).

How common is TCAP p.Cys8= (c.24C>T) in the general population?

TCAP p.Cys8= (c.24C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

TCAP p.Cys8=

c.24C>T · rs756548785 · VCV464946

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Conditions

familial hypertrophic cardiomyopathy

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 -0.098	GERP -1.1, phastCons 0.5
Overall
CADD	11.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,076 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00174% 28/1,613,500 alleles · ultra-rare exomes 26/1,461,472 · genomes 2/152,028 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,108
Admixed American	0.00333%	29,993
African / African-American	0.00267%	37,427
Remaining individualsnot grpmax-eligible	0.0016%	62,466
European (non-Finnish)	0.0011%	90,764

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.Cys8=
Coding: c.24C>T
MANE Select: NM_003673
dbSNP: rs756548785
Type: single nucleotide variant
Location: chr17:39665383 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 8: a β-strand

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: hypertrophic cardiomyopathy 25

Similar variants

TCAP p.Cys8Arg Uncertain significance ★ ⚠ same residue
TCAP p.Cys8Phe Uncertain significance ★ ⚠ same residue
TCAP p.Cys8Ser Uncertain significance ★ ⚠ 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

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-cys8 (accessed [today's date]).

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