Is TPM3 p.Arg161= (c.483G>A) pathogenic?

TPM3 p.Arg161= (c.483G>A) is classified Likely benign in TPM3 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-17). Very rare (popmax 0.00934%, afr); Associated with congenital myopathy 4B, autosomal recessive.

What condition is associated with TPM3 p.Arg161= (c.483G>A)?

TPM3 p.Arg161= (c.483G>A) is associated with congenital myopathy 4B, autosomal recessive, congenital fiber-type disproportion myopathy (ClinVar).

How common is TPM3 p.Arg161= (c.483G>A) in the general population?

TPM3 p.Arg161= (c.483G>A) is very rare (popmax 0.00934%, afr) (gnomAD).

How is Intermediate nemaline myopathy inherited?

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

TPM3 p.Arg161=

c.483G>A · rs150586027 · VCV531182

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Conditions

congenital myopathy 4B, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.69 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.38	phastCons 0.99
Overall
CADD	11.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,948 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000434% 7/1,614,106 alleles · very rare exomes 5/1,461,884 · genomes 2/152,222 · 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: TPM3
Protein: p.Arg161=
Coding: c.483G>A
MANE Select: NM_152263
dbSNP: rs150586027
Type: single nucleotide variant
Location: chr1:154173096 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 91.69 · 1 PDB

Full TPM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myopathy 4B, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital fiber-type disproportion myopathy

For Intermediate nemaline myopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

TPM3 c.118-12G>A Pathogenic/Likely pathogenic ★★ same condition
TPM3 p.Ala152Val Pathogenic/Likely pathogenic ★★ same condition
TPM3 p.Arg168Cys Pathogenic ★★ same condition
TPM3 p.Arg168Gly Pathogenic/Likely pathogenic ★★ same condition
TPM3 p.Arg168His Pathogenic ★★ same condition
TPM3 p.Arg91Cys Pathogenic/Likely pathogenic ★★ same condition
TPM3 p.Arg91His Likely pathogenic ★★ same condition
TPM3 p.Gln32Ter 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/tpm3-p-arg161 (accessed [today's date]).

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