Is TPM2 p.Ser271= (c.813C>T) pathogenic?

TPM2 p.Ser271= (c.813C>T) is classified Benign/Likely benign in TPM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-17). Rare (popmax 0.243%, eas); Associated with congenital myopathy 23.

What condition is associated with TPM2 p.Ser271= (c.813C>T)?

TPM2 p.Ser271= (c.813C>T) is associated with congenital myopathy 23, arthrogryposis, distal, type 1A (ClinVar).

How common is TPM2 p.Ser271= (c.813C>T) in the general population?

TPM2 p.Ser271= (c.813C>T) is rare (popmax 0.243%, eas) (gnomAD).

How is Typical nemaline myopathy inherited?

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

TPM2 p.Ser271=

c.813C>T · rs201215303 · VCV366767

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.243%, eas)

Conditions

congenital myopathy 23

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 -1.1	GERP -3.8
Overall
CADD	4.979	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.243% East Asian · 101/41,540 alleles

Filtering AF 0.205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.19%

Overall 0.00687% 107/1,556,782 alleles · rare exomes 98/1,404,784 · genomes 9/151,998 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.243%	411
Admixed American	0.0019%	52,518
South Asian	0.00118%	84,938
European (non-Finnish)	0.000348%	287,176

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: TPM2
Protein: p.Ser271=
Coding: c.813C>T
MANE Select: NM_003289
dbSNP: rs201215303
Type: single nucleotide variant
Location: chr9:35683201 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 91.51
Residue 271: a modified residue (phosphoserine)

Full TPM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myopathy 23 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: arthrogryposis, distal, type 1A

For Typical nemaline myopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

TPM2 p.Ser271Ile Uncertain significance ★ ⚠ same residue
TPM2 p.Ala155Thr Pathogenic/Likely pathogenic ★★ same condition
TPM2 p.Arg133Trp Pathogenic ★★ same condition
TPM2 p.Gln24Ter Pathogenic/Likely pathogenic ★★ same condition
TPM2 p.Gln9Pro Likely pathogenic ★★ same condition
TPM2 p.Glu117Lys Pathogenic/Likely pathogenic ★★ same condition
TPM2 p.Lys128Glu Likely pathogenic ★★ same condition
TPM2 p.Tyr261Cys 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/tpm2-p-ser271 (accessed [today's date]).

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