Is TPM1 p.Val44= (c.132G>A) pathogenic?

TPM1 p.Val44= (c.132G>A) is classified Likely benign in TPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). Absent from gnomAD v4.1; Associated with hypertrophic cardiomyopathy.

What condition is associated with TPM1 p.Val44= (c.132G>A)?

TPM1 p.Val44= (c.132G>A) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is TPM1 p.Val44= (c.132G>A) in the general population?

TPM1 p.Val44= (c.132G>A) is absent from gnomAD v4.1 (gnomAD).

TPM1 p.Val44=

c.132G>A · rs2140627644 · VCV1592319

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hypertrophic cardiomyopathy

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 4.8	GERP -0.18, phastCons 1
Overall
CADD	12.22	PHRED · no single calibrated threshold — expert panels disagree

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: TPM1
Protein: p.Val44=
Coding: c.132G>A
MANE Select: NM_001018005
dbSNP: rs2140627644
Type: single nucleotide variant
Location: chr15:63044044 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.67 · 14 PDB

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

Disease context

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

Similar variants

TPM1 p.Val44Ala Uncertain significance ★★ ⚠ same residue
TPM1 p.Val44Met Uncertain significance ★★ ⚠ same residue
TPM1 p.Val44Gly 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

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-val44 (accessed [today's date]).

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