Is TCAP p.Arg70Gln (c.209G>A) pathogenic?

TCAP p.Arg70Gln (c.209G>A) is classified Uncertain significance in TCAP (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.1107); Ultra-rare (popmax 0.0371%, amr); Associated with Cardiovascular phenotype.

What condition is associated with TCAP p.Arg70Gln (c.209G>A)?

TCAP p.Arg70Gln (c.209G>A) is associated with Cardiovascular phenotype, autosomal recessive limb-girdle muscular dystrophy type 2G, hypertrophic cardiomyopathy 25 (ClinVar).

How common is TCAP p.Arg70Gln (c.209G>A) in the general population?

TCAP p.Arg70Gln (c.209G>A) is ultra-rare (popmax 0.0371%, amr) (gnomAD).

What do computational predictors say about TCAP p.Arg70Gln (c.209G>A)?

AlphaMissense predicts likely benign (score 0.1107) — an in-silico prediction, not a clinical call.

TCAP p.Arg70Gln

c.209G>A · rs552865793 · VCV202110

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.1107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0371%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1107	likely benign
REVEL	0.653	pathogenic-leaning
SaProt	LLR -7.54	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
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	29.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0371% Admixed American · 22/59,262 alleles

Filtering AF 0.0251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0211%

Overall 0.00373% 60/1,606,842 alleles · ultra-rare exomes 43/1,454,694 · genomes 17/152,148 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0371%	2,694
Remaining individualsnot grpmax-eligible	0.0177%	5,650
Ashkenazi Jewishnot grpmax-eligible	0.00341%	29,354
European (non-Finnish)	0.00204%	49,029
African / African-American	0.00134%	74,824
South Asian	0.00111%	90,378

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.Arg70Gln
Coding: c.209G>A
MANE Select: NM_003673
dbSNP: rs552865793
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

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

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2G hypertrophic cardiomyopathy 25 familial hypertrophic cardiomyopathy

Similar variants

TCAP p.Arg70Trp Uncertain significance ★★ ⚠ same residue
TCAP p.Arg70= Likely benign ★★ same residue
TCAP p.Arg70Pro Uncertain significance ★ ⚠ same residue
TCAP c.110+5G>T Likely pathogenic ★★ same condition
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

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-arg70gln (accessed [today's date]).

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