Is TCAP p.Pro65= (c.195C>T) pathogenic?

TCAP p.Pro65= (c.195C>T) is classified Likely benign in TCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). Very rare (popmax 0.000425%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TCAP p.Pro65= (c.195C>T)?

TCAP p.Pro65= (c.195C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is TCAP p.Pro65= (c.195C>T) in the general population?

TCAP p.Pro65= (c.195C>T) is very rare (popmax 0.000425%, nfe) (gnomAD).

TCAP p.Pro65=

c.195C>T · rs370118201 · VCV2447685

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000425%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.13	GERP -2.1, phastCons 0.93
Overall
CADD	8.124	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000425% European (non-Finnish) · 5/1,177,472 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000311% 5/1,608,000 alleles · very rare exomes 5/1,455,672 · genomes 0/152,328 · joint denominator

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.Pro65=
Coding: c.195C>T
MANE Select: NM_003673
dbSNP: rs370118201
Type: single nucleotide variant
Location: chr17:39665800 (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.Pro65Leu 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-pro65 (accessed [today's date]).

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