Is TCAP p.Phe21del (c.62_64del) pathogenic?

TCAP p.Phe21del (c.6264del) is classified Uncertain significance in TCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-13). Very rare (popmax 0.00669%, eas); Associated with hypertrophic cardiomyopathy 25.

What condition is associated with TCAP p.Phe21del (c.62_64del)?

TCAP p.Phe21del (c.62_64del) is associated with hypertrophic cardiomyopathy 25, familial hypertrophic cardiomyopathy (ClinVar).

How common is TCAP p.Phe21del (c.62_64del) in the general population?

TCAP p.Phe21del (c.62_64del) is very rare (popmax 0.00669%, eas) (gnomAD).

TCAP p.Phe21del

c.62_64del · rs1373067817 · VCV2927814

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

hypertrophic cardiomyopathy 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP -0.059, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,872 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000186% 3/1,613,726 alleles · very rare exomes 3/1,461,476 · genomes 0/152,250 · joint denominator

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.Phe21del
Coding: c.62_64del
MANE Select: NM_003673
dbSNP: rs1373067817
Type: Deletion
Location: chr17:39665419 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 21: a β-strand

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

Disease context

hypertrophic cardiomyopathy 25 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypertrophic cardiomyopathy

Similar variants

TCAP c.110_110+1del Pathogenic ★★ same condition
TCAP p.Ile111fs Uncertain significance ★★ same condition
TCAP p.Gln46fs Pathogenic ★ same condition
TCAP p.Glu12fs Pathogenic ★ same condition
TCAP p.Tyr51fs Pathogenic ★ same condition
TCAP p.Arg153fs Uncertain significance ★ same condition
TCAP p.Glu135fs Uncertain significance ★ same condition
TCAP p.Met160fs 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-phe21del (accessed [today's date]).

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