Is TCAP p.Arg70= (c.208C>A) pathogenic?

TCAP p.Arg70= (c.208C>A) is classified Likely benign in TCAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-16). Ultra-rare (popmax 0.0167%, mid); Associated with Cardiovascular phenotype.

What condition is associated with TCAP p.Arg70= (c.208C>A)?

TCAP p.Arg70= (c.208C>A) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy 25, familial hypertrophic cardiomyopathy (ClinVar).

How common is TCAP p.Arg70= (c.208C>A) in the general population?

TCAP p.Arg70= (c.208C>A) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

TCAP p.Arg70=

c.208C>A · rs775636212 · VCV1078254

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Conditions

Cardiovascular phenotype

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 2.7	GERP 2.6, phastCons 1
Overall
CADD	14.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/5,986 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000187% 3/1,606,450 alleles · ultra-rare exomes 3/1,454,208 · genomes 0/152,242 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,986
European (non-Finnish)	0.00017%	588,218

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.Arg70=
Coding: c.208C>A
MANE Select: NM_003673
dbSNP: rs775636212
Type: single nucleotide variant
Location: chr17:39665813 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 25 familial hypertrophic cardiomyopathy

Similar variants

TCAP p.Arg70Gln Uncertain significance ★★ ⚠ same residue
TCAP p.Arg70Trp Uncertain significance ★★ ⚠ same residue
TCAP p.Arg70Pro 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

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-arg70 (accessed [today's date]).

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