Is TCAP p.Ser147= (c.441C>T) pathogenic?

TCAP p.Ser147= (c.441C>T) is classified Likely benign in TCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). Ultra-rare (popmax 0.0164%, mid); Associated with hypertrophic cardiomyopathy 25.

What condition is associated with TCAP p.Ser147= (c.441C>T)?

TCAP p.Ser147= (c.441C>T) is associated with hypertrophic cardiomyopathy 25, familial hypertrophic cardiomyopathy (ClinVar).

How common is TCAP p.Ser147= (c.441C>T) in the general population?

TCAP p.Ser147= (c.441C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

TCAP p.Ser147=

c.441C>T · rs1380602024 · VCV966581

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 · no allele here is in the release
Pangolin	Δ0.35	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6	GERP 2.6, phastCons 1
Overall
CADD	13.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Overall 0.000124% 2/1,608,688 alleles · ultra-rare exomes 1/1,456,468 · genomes 1/152,220 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
East Asian	0.00223%	44,894

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.Ser147=
Coding: c.441C>T
MANE Select: NM_003673
dbSNP: rs1380602024
Type: single nucleotide variant
Location: chr17:39666046 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 147: the 'disordered' region

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 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-ser147 (accessed [today's date]).

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