Is CSRP3 p.Thr84= (c.252G>A) pathogenic?

CSRP3 p.Thr84= (c.252G>A) is classified Likely benign in CSRP3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-10). Ultra-rare (popmax 0.0497%, mid); Associated with Cardiovascular phenotype.

What condition is associated with CSRP3 p.Thr84= (c.252G>A)?

CSRP3 p.Thr84= (c.252G>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1M (ClinVar).

How common is CSRP3 p.Thr84= (c.252G>A) in the general population?

CSRP3 p.Thr84= (c.252G>A) is ultra-rare (popmax 0.0497%, mid) (gnomAD).

CSRP3 p.Thr84=

c.252G>A · rs755614464 · VCV389630

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, mid)

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 -12	GERP -14
Overall
CADD	0.363	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0497% Middle Eastern · 3/6,042 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0072%

Overall 0.00341% 55/1,614,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0497%	2,014
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,402
South Asian	0.00988%	10,120
Admixed American	0.00667%	15,002
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.00246%	40,691
East Asian	0.00223%	44,894
African / African-American	0.00133%	74,926

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.Thr84=
Coding: c.252G>A
MANE Select: NM_003476
dbSNP: rs755614464
Type: single nucleotide variant
Location: chr11:19188165 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB

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: cardiomyopathy dilated cardiomyopathy 1M hypertrophic cardiomyopathy 12

Similar variants

CSRP3 p.Thr84Met Uncertain significance ★★ ⚠ same residue
CSRP3 p.Thr84Arg 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

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-thr84 (accessed [today's date]).

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