Is TCAP p.Pro90= (c.270G>A) pathogenic?

TCAP p.Pro90= (c.270G>A) is classified Conflicting classifications of pathogenicity in TCAP (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-04-27). Ultra-rare (popmax 0.064%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TCAP p.Pro90= (c.270G>A)?

TCAP p.Pro90= (c.270G>A) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy 25, familial hypertrophic cardiomyopathy (ClinVar).

How common is TCAP p.Pro90= (c.270G>A) in the general population?

TCAP p.Pro90= (c.270G>A) is ultra-rare (popmax 0.064%, afr) (gnomAD).

TCAP p.Pro90=

c.270G>A · rs372538567 · VCV195198

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.064%, afr)

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 -14	GERP -5.3
Overall
CADD	0.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.064% African / African-American · 48/75,026 alleles

Filtering AF 0.0495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0444%

Overall 0.0036% 58/1,611,372 alleles · ultra-rare exomes 35/1,459,084 · genomes 23/152,288 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.064%	1,563
Remaining individualsnot grpmax-eligible	0.0032%	31,203
East Asian	0.00223%	44,836
South Asian	0.0022%	45,445
Admixed American	0.00167%	59,782
European (non-Finnish)	0.000339%	294,859

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.Pro90=
Coding: c.270G>A
MANE Select: NM_003673
dbSNP: rs372538567
Type: single nucleotide variant
Location: chr17:39665875 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 90: a UniProt-annotated variant site (in cmh25; uncertain significance)

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.Pro90Leu Uncertain significance ★★ ⚠ same residue
TCAP p.Pro90Gln 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-pro90 (accessed [today's date]).

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