Is CSRP3 p.Thr33= (c.99G>A) pathogenic?

CSRP3 p.Thr33= (c.99G>A) is classified Conflicting classifications of pathogenicity in CSRP3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-03-02). Very rare (popmax 0.00446%, eas); Associated with Cardiovascular phenotype.

What condition is associated with CSRP3 p.Thr33= (c.99G>A)?

CSRP3 p.Thr33= (c.99G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1M, hypertrophic cardiomyopathy 12 (ClinVar).

How common is CSRP3 p.Thr33= (c.99G>A) in the general population?

CSRP3 p.Thr33= (c.99G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

CSRP3 p.Thr33=

c.99G>A · rs147549410 · VCV726293

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 2.7	GERP 2.8, phastCons 1
Overall
CADD	11.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,890 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00136% 22/1,613,690 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,445
African / African-American	0.004%	24,972
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.00329%	30,359
Remaining individualsnot grpmax-eligible	0.0032%	31,235
Finnishnot grpmax-eligible	0.00156%	64,018
European (non-Finnish)	0.000848%	117,973

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: CSRP3
Protein: p.Thr33=
Coding: c.99G>A
MANE Select: NM_003476
dbSNP: rs147549410
Type: single nucleotide variant
Location: chr11:19192350 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 33: the lim zinc-binding 1 domain; a turn

Full CSRP3 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: dilated cardiomyopathy 1M hypertrophic cardiomyopathy 12

Similar variants

CSRP3 p.Thr33Met Uncertain significance ★★ ⚠ same residue
CSRP3 c.414+1G>T Likely pathogenic ★★ same condition
CSRP3 p.Cys37Ter Pathogenic/Likely pathogenic ★★ same condition
CSRP3 p.Cys58Gly Pathogenic ★★ same condition
CSRP3 p.Lys113Ter Pathogenic ★★ same condition
CSRP3 c.113-3C>T Uncertain significance ★★ same condition
CSRP3 c.414+6A>G Uncertain significance ★★ same condition
CSRP3 c.415-1G>A 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/csrp3-p-thr33 (accessed [today's date]).

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