Is TPM2 p.Asp100= (c.300C>T) pathogenic?

TPM2 p.Asp100= (c.300C>T) is classified Benign/Likely benign in TPM2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-22). Rare (popmax 0.645%, sas); Associated with arthrogryposis, distal, type 1A.

What condition is associated with TPM2 p.Asp100= (c.300C>T)?

TPM2 p.Asp100= (c.300C>T) is associated with arthrogryposis, distal, type 1A (ClinVar).

How common is TPM2 p.Asp100= (c.300C>T) in the general population?

TPM2 p.Asp100= (c.300C>T) is rare (popmax 0.645%, sas) (gnomAD).

TPM2 p.Asp100=

c.300C>T · rs532190742 · VCV259036

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.645%, sas)

Conditions

arthrogryposis, distal, type 1A

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 3.4	GERP -0.27, phastCons 1
Overall
CADD	11.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.645% South Asian · 587/91,078 alleles

Filtering AF 0.601% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.584%

Overall 0.0382% 616/1,614,148 alleles · rare exomes 589/1,461,886 · genomes 27/152,262 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.645%	155
Remaining individualsnot grpmax-eligible	0.032%	3,126
European (non-Finnish)	0.000763%	131,116

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.Asp100=
Coding: c.300C>T
MANE Select: NM_003289
dbSNP: rs532190742
Type: single nucleotide variant
Location: chr9:35685721 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 91.51

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

Disease context

arthrogryposis, distal, type 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
TPM2 c.240+5G>T Uncertain significance ★★ 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-asp100 (accessed [today's date]).

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