Is TCAP p.Glu80Asp (c.240G>T) pathogenic?

TCAP p.Glu80Asp (c.240G>T) is classified Uncertain significance in TCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-17). AlphaMissense: likely benign (0.3043); Very rare (popmax 0.000248%); Associated with hypertrophic cardiomyopathy 25.

What condition is associated with TCAP p.Glu80Asp (c.240G>T)?

TCAP p.Glu80Asp (c.240G>T) is associated with hypertrophic cardiomyopathy 25, familial hypertrophic cardiomyopathy (ClinVar).

How common is TCAP p.Glu80Asp (c.240G>T) in the general population?

TCAP p.Glu80Asp (c.240G>T) is very rare (popmax 0.000248%) (gnomAD).

What do computational predictors say about TCAP p.Glu80Asp (c.240G>T)?

AlphaMissense predicts likely benign (score 0.3043) — an in-silico prediction, not a clinical call.

TCAP p.Glu80Asp

c.240G>T · rs758101613 · VCV497495

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3043 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000248%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hypertrophic cardiomyopathy 25

Computational evidence

Protein change
AlphaMissense	0.3043	likely benign
REVEL	0.626	indeterminate
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -3.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 746 bp · p 0.44 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000248%

Overall 0.000248% 4/1,609,812 alleles · very rare exomes 4/1,457,468 · genomes 0/152,344 · 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.Glu80Asp
Coding: c.240G>T
MANE Select: NM_003673
dbSNP: rs758101613
Type: single nucleotide variant
Location: chr17:39665845 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 80: 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 p.Glu80= Likely benign ★★ same residue
TCAP p.Glu80Gly 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-glu80asp (accessed [today's date]).

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