Is TCAP p.Pro142= (c.426T>G) pathogenic?

TCAP p.Pro142= (c.426T>G) is classified Likely benign in TCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-19). Very rare (popmax 0.000509%, nfe); Associated with hypertrophic cardiomyopathy 25.

What condition is associated with TCAP p.Pro142= (c.426T>G)?

TCAP p.Pro142= (c.426T>G) is associated with hypertrophic cardiomyopathy 25, familial hypertrophic cardiomyopathy (ClinVar).

How common is TCAP p.Pro142= (c.426T>G) in the general population?

TCAP p.Pro142= (c.426T>G) is very rare (popmax 0.000509%, nfe) (gnomAD).

TCAP p.Pro142=

c.426T>G · rs1397854344 · VCV1628087

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

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
Constraint at this position
Conservation	phyloP -20	GERP -5.3
Overall
CADD	0.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,904 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000373% 6/1,610,292 alleles · very rare exomes 6/1,458,000 · genomes 0/152,292 · 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.Pro142=
Coding: c.426T>G
MANE Select: NM_003673
dbSNP: rs1397854344
Type: single nucleotide variant
Location: chr17:39666031 (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.Pro142Thr Uncertain significance ★ ⚠ same residue
TCAP p.Pro142fs 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

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-pro142 (accessed [today's date]).

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