Is TCAP p.Ter168= (c.504AG[1]) pathogenic?

TCAP p.Ter168= (c.504AG[1]) is classified Uncertain significance in TCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-06). Very rare (popmax 8.48e-05%, nfe); Associated with hypertrophic cardiomyopathy 25.

What condition is associated with TCAP p.Ter168= (c.504AG[1])?

TCAP p.Ter168= (c.504AG[1]) is associated with hypertrophic cardiomyopathy 25, familial hypertrophic cardiomyopathy (ClinVar).

How common is TCAP p.Ter168= (c.504AG[1]) in the general population?

TCAP p.Ter168= (c.504AG[1]) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

TCAP p.Ter168=

c.504AG[1] · rs2057253961 · VCV1046017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hypertrophic cardiomyopathy 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,888 alleles

Overall 6.25e-05% 1/1,599,636 alleles · very rare exomes 1/1,447,396 · genomes 0/152,240 · 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.Ter168=
Coding: c.504AG[1]
MANE Select: NM_003673
dbSNP: rs2057253961
Type: Microsatellite
Location: chr17:39666108 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB

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.Glu105del Uncertain significance ★★ same condition
TCAP p.Glu43del Uncertain significance ★★ same condition
TCAP p.Arg18fs Pathogenic ★ same condition
TCAP p.Cys15_Glu16delinsTer Pathogenic ★ same condition
TCAP p.Glu13del Conflicting classifications of pathogenicity ★ same condition
TCAP p.Met69del Uncertain significance ★ same condition
TCAP p.Glu120fs Likely pathogenic same condition
TCAP p.Ter168Trp Uncertain significance same residue

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-ter168 (accessed [today's date]).

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