Is TPM1 p.Ser271= (c.813C>T) pathogenic?

TPM1 p.Ser271= (c.813C>T) is classified Likely benign in TPM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-05). Very rare (popmax 0.0011%, sas); Associated with Cardiovascular phenotype.

What condition is associated with TPM1 p.Ser271= (c.813C>T)?

TPM1 p.Ser271= (c.813C>T) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy (ClinVar).

How common is TPM1 p.Ser271= (c.813C>T) in the general population?

TPM1 p.Ser271= (c.813C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

TPM1 p.Ser271=

c.813C>T · rs1313357866 · VCV2196905

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Cardiovascular phenotype

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	GERP 1.9, phastCons 1
Overall
CADD	14.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,046 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,614,104 alleles · very rare exomes 7/1,461,804 · genomes 0/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,046
European (non-Finnish)	0.000508%	196,670

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.Ser271=
Coding: c.813C>T
MANE Select: NM_001018005
dbSNP: rs1313357866
Type: single nucleotide variant
Location: chr15:63064104 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.67 · 14 PDB
Residue 271: a modified residue (phosphoserine)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy

Similar variants

TPM1 p.Ser271Asn Uncertain significance ★★ ⚠ same residue
TPM1 p.Ser271Arg Uncertain significance ★ ⚠ same residue
TPM1 p.Ser271Ile 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-ser271 (accessed [today's date]).

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