Is TCAP p.Arg70Pro (c.209G>C) pathogenic?

TCAP p.Arg70Pro (c.209G>C) is classified Uncertain significance in TCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-12). AlphaMissense: likely pathogenic (0.9003); Absent from gnomAD v4.1; Associated with familial hypertrophic cardiomyopathy.

What condition is associated with TCAP p.Arg70Pro (c.209G>C)?

TCAP p.Arg70Pro (c.209G>C) is associated with familial hypertrophic cardiomyopathy, hypertrophic cardiomyopathy 25 (ClinVar).

How common is TCAP p.Arg70Pro (c.209G>C) in the general population?

TCAP p.Arg70Pro (c.209G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TCAP p.Arg70Pro (c.209G>C)?

AlphaMissense predicts likely pathogenic (score 0.9003) — an in-silico prediction, not a clinical call.

TCAP p.Arg70Pro

c.209G>C · VCV4784415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9003 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.9003	likely pathogenic · top 1% in TCAP
REVEL	0.734	pathogenic-leaning
SaProt	LLR -11.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 746 bp · p 0.44 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TCAP
Protein: p.Arg70Pro
Coding: c.209G>C
MANE Select: NM_003673
Type: single nucleotide variant
Location: chr17:39665814 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 70: a β-strand; a UniProt-annotated variant site (in cmh25)

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.Arg70Gln Uncertain significance ★★ ⚠ same residue
TCAP p.Arg70Trp Uncertain significance ★★ ⚠ same residue
TCAP p.Arg70= Likely benign ★★ 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

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-arg70pro (accessed [today's date]).

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