Is TCAP p.Leu28= (c.82C>T) pathogenic?

TCAP p.Leu28= (c.82C>T) is classified Likely benign in TCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-21). Very rare (popmax 0.0011%, sas); Associated with Cardiovascular phenotype.

What condition is associated with TCAP p.Leu28= (c.82C>T)?

TCAP p.Leu28= (c.82C>T) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy 25, familial hypertrophic cardiomyopathy (ClinVar).

How common is TCAP p.Leu28= (c.82C>T) in the general population?

TCAP p.Leu28= (c.82C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

TCAP p.Leu28=

c.82C>T · rs747005525 · VCV1762818

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Cardiovascular phenotype

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 1.4	GERP -0.19, phastCons 0.8
Overall
CADD	8.993	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,070 alleles

Overall 0.000124% 2/1,613,562 alleles · very rare exomes 2/1,461,322 · genomes 0/152,240 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,070
European (non-Finnish)	8.48e-05%	1,179,916

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.Leu28=
Coding: c.82C>T
MANE Select: NM_003673
dbSNP: rs747005525
Type: single nucleotide variant
Location: chr17:39665441 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 28: a β-strand

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.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
TCAP c.*292G>A Uncertain significance ★★ same condition
TCAP c.*297C>T 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-leu28 (accessed [today's date]).

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