Is TCAP p.Ala20= (c.60C>G) pathogenic?

TCAP p.Ala20= (c.60C>G) is classified Conflicting classifications of pathogenicity in TCAP (ClinVar, Conflicting submitters, 17 submitters; last evaluated 2026-05-01). Ultra-rare (popmax 0.033%, nfe); Associated with hypertrophic cardiomyopathy 25.

What condition is associated with TCAP p.Ala20= (c.60C>G)?

TCAP p.Ala20= (c.60C>G) is associated with hypertrophic cardiomyopathy 25, autosomal recessive limb-girdle muscular dystrophy type 2G, familial hypertrophic cardiomyopathy (ClinVar).

How common is TCAP p.Ala20= (c.60C>G) in the general population?

TCAP p.Ala20= (c.60C>G) is ultra-rare (popmax 0.033%, nfe) (gnomAD).

TCAP p.Ala20=

c.60C>G · rs146502276 · VCV44714

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, 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 0.8	GERP 0.13, phastCons 1
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% European (non-Finnish) · 389/1,179,954 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0292%

Overall 0.0253% 408/1,613,608 alleles · ultra-rare exomes 361/1,461,468 · genomes 47/152,140 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.033%	3,033
Finnishnot grpmax-eligible	0.0141%	7,082
Remaining individualsnot grpmax-eligible	0.0128%	7,808
Admixed American	0.00333%	30,001

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.Ala20=
Coding: c.60C>G
MANE Select: NM_003673
dbSNP: rs146502276
Type: single nucleotide variant
Location: chr17:39665419 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 20: 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: autosomal recessive limb-girdle muscular dystrophy type 2G familial hypertrophic cardiomyopathy

Similar variants

TCAP p.Ala20Ser 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
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-ala20 (accessed [today's date]).

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