Is TPM1 p.Asp2= (c.6C>T) pathogenic?

TPM1 p.Asp2= (c.6C>T) is classified Conflicting classifications of pathogenicity in TPM1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-07). Ultra-rare (popmax 0.0134%, eas); Associated with dilated cardiomyopathy 1Y.

What condition is associated with TPM1 p.Asp2= (c.6C>T)?

TPM1 p.Asp2= (c.6C>T) is associated with dilated cardiomyopathy 1Y, hypertrophic cardiomyopathy, hypertrophic cardiomyopathy 3 (ClinVar).

How common is TPM1 p.Asp2= (c.6C>T) in the general population?

TPM1 p.Asp2= (c.6C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

How is Left ventricular noncompaction inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TPM1 p.Asp2=

c.6C>T · rs1350935943 · VCV887085

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

dilated cardiomyopathy 1Y

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 4.7	GERP 1.9, phastCons 1
Overall
CADD	17.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,836 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000496% 8/1,612,984 alleles · ultra-rare exomes 7/1,460,772 · genomes 1/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,473
Finnishnot grpmax-eligible	0.00156%	63,956
European (non-Finnish)	8.48e-05%	1,179,313

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: TPM1
Protein: p.Asp2=
Coding: c.6C>T
MANE Select: NM_001018005
dbSNP: rs1350935943
Type: single nucleotide variant
Location: chr15:63042835 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.67 · 14 PDB
Residue 2: the 'disordered' region; an α-helix

Full TPM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 1Y — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy hypertrophic cardiomyopathy 3

For Left ventricular noncompaction (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages

Similar variants

TPM1 p.Asp2His Uncertain significance ★★ ⚠ same residue
TPM1 p.Ala183Val Uncertain significance ★★★ ⚠ same condition
TPM1 p.Met281Thr Uncertain significance ★★★ ⚠ same condition
TPM1 p.Thr108Ile Uncertain significance ★★★ ⚠ same condition
TPM1 p.Lys266Arg Likely benign ★★★ ⚠ same condition
TPM1 p.Thr282Ser Benign ★★★ same condition
TPM1 p.Ala63Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
TPM1 p.Arg160His Pathogenic/Likely pathogenic ★★ ⚠ 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/tpm1-p-asp2 (accessed [today's date]).

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