Is TCAP p.Lys98= (c.294G>A) pathogenic?

TCAP p.Lys98= (c.294G>A) is classified Likely benign in TCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-29). Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TCAP p.Lys98= (c.294G>A)?

TCAP p.Lys98= (c.294G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is TCAP p.Lys98= (c.294G>A) in the general population?

TCAP p.Lys98= (c.294G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

TCAP p.Lys98=

c.294G>A · VCV4865374

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, 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 4.4	GERP 0.39, phastCons 1
Overall
CADD	8.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,918 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00149% 24/1,612,524 alleles · very rare exomes 21/1,460,336 · genomes 3/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,459
European (non-Finnish)	0.00178%	56,185
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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.Lys98=
Coding: c.294G>A
MANE Select: NM_003673
Type: single nucleotide variant
Location: chr17:39665899 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB

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

Similar variants

TCAP p.Lys98Arg Uncertain significance ★★ ⚠ same residue
TCAP p.Gln53Ter Pathogenic/Likely pathogenic ★★ same condition
TCAP c.110+4A>G Uncertain significance ★★ same condition
TCAP p.Arg130His Uncertain significance ★★ ⚠ same condition
TCAP p.Arg153Ser Uncertain significance ★★ ⚠ same condition
TCAP p.Arg154Cys Uncertain significance ★★ ⚠ same condition
TCAP p.Arg154Ser Uncertain significance ★★ same condition
TCAP p.Arg158Gly 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-lys98 (accessed [today's date]).

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