Is TCAP p.Ser39= (c.117C>T) pathogenic?

TCAP p.Ser39= (c.117C>T) is classified Likely benign in TCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-29). Very rare (popmax 0.00335%, amr); Associated with familial hypertrophic cardiomyopathy.

What condition is associated with TCAP p.Ser39= (c.117C>T)?

TCAP p.Ser39= (c.117C>T) is associated with familial hypertrophic cardiomyopathy, hypertrophic cardiomyopathy 25 (ClinVar).

How common is TCAP p.Ser39= (c.117C>T) in the general population?

TCAP p.Ser39= (c.117C>T) is very rare (popmax 0.00335%, amr) (gnomAD).

TCAP p.Ser39=

c.117C>T · rs759893644 · VCV1585506

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00335%, amr)

Conditions

familial hypertrophic cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.12	GERP -5.2, phastCons 0.11
Overall
CADD	6.172	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00335% Admixed American · 2/59,712 alleles

Filtering AF 0.000556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000807% 13/1,610,128 alleles · very rare exomes 13/1,457,818 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00335%	29,856
Finnishnot grpmax-eligible	0.0016%	62,574
European (non-Finnish)	0.000848%	117,895

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.Ser39=
Coding: c.117C>T
MANE Select: NM_003673
dbSNP: rs759893644
Type: single nucleotide variant
Location: chr17:39665722 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 39: a β-strand; a modified residue (phosphoserine)

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.Ser39Cys 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
TCAP c.110+4A>G Uncertain significance ★★ same condition
TCAP c.*292G>A 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-ser39 (accessed [today's date]).

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