Is TCAP p.Cys15Ser (c.43T>A) pathogenic?

TCAP p.Cys15Ser (c.43T>A) is classified Uncertain significance in TCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-09). AlphaMissense: likely benign (0.0736); Ultra-rare (popmax 0.0165%, sas); Associated with Cardiovascular phenotype.

What condition is associated with TCAP p.Cys15Ser (c.43T>A)?

TCAP p.Cys15Ser (c.43T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is TCAP p.Cys15Ser (c.43T>A) in the general population?

TCAP p.Cys15Ser (c.43T>A) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about TCAP p.Cys15Ser (c.43T>A)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

TCAP p.Cys15Ser

c.43T>A · rs764350236 · VCV3175036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -3.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.64 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.63	GERP -3.9
Regional constraint	o/e 0.95	unconstrained · MANE · 746 bp · p 0.44 · regional, not allelic
Overall
CADD	5.033	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,068 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.000992% 16/1,613,664 alleles · ultra-rare exomes 16/1,461,516 · genomes 0/152,148 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,071
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Cys15Ser
Coding: c.43T>A
MANE Select: NM_003673
dbSNP: rs764350236
Type: single nucleotide variant
Location: chr17:39665402 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 15: a turn

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.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
TCAP p.Arg18Gln 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-cys15ser (accessed [today's date]).

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