Is TCAP p.Ile73Val (c.217A>G) pathogenic?

TCAP p.Ile73Val (c.217A>G) is classified Uncertain significance in TCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-29). AlphaMissense: likely benign (0.1258); Absent from gnomAD v4.1.

How common is TCAP p.Ile73Val (c.217A>G) in the general population?

TCAP p.Ile73Val (c.217A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TCAP p.Ile73Val (c.217A>G)?

AlphaMissense predicts likely benign (score 0.1258) — an in-silico prediction, not a clinical call.

TCAP p.Ile73Val

c.217A>G · rs2543739248 · VCV2436993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1258 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1258	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -5.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP 0.65, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 746 bp · p 0.44 · regional, not allelic
Overall
CADD	14.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TCAP
Protein: p.Ile73Val
Coding: c.217A>G
MANE Select: NM_003673
dbSNP: rs2543739248
Type: single nucleotide variant
Location: chr17:39665822 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 73: a β-strand

Full TCAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TCAP p.Ile73Thr Uncertain significance ★ ⚠ same residue
TCAP c.110+5G>T Likely pathogenic ★★ same type
TCAP p.Cys57Ter Pathogenic/Likely pathogenic ★★ same type
TCAP p.Gln53Ter Pathogenic/Likely pathogenic ★★ same type
TCAP p.Glu35Ter Pathogenic ★★ same type
TCAP p.Trp22Ter Pathogenic/Likely pathogenic ★★ same type
TCAP p.Trp25Ter Pathogenic/Likely pathogenic ★★ same type
TCAP c.110+4A>G Uncertain significance ★★ same type

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-ile73val (accessed [today's date]).

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