Is CSRP3 p.Val127Ile (c.379G>A) pathogenic?

CSRP3 p.Val127Ile (c.379G>A) is classified Uncertain significance in CSRP3 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-14). AlphaMissense: ambiguous (0.4026); Very rare (popmax 0.00934%, afr); Associated with Cardiovascular phenotype.

What condition is associated with CSRP3 p.Val127Ile (c.379G>A)?

CSRP3 p.Val127Ile (c.379G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1M, hypertrophic cardiomyopathy 12 (ClinVar).

How common is CSRP3 p.Val127Ile (c.379G>A) in the general population?

CSRP3 p.Val127Ile (c.379G>A) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about CSRP3 p.Val127Ile (c.379G>A)?

AlphaMissense predicts ambiguous (score 0.4026) — an in-silico prediction, not a clinical call.

CSRP3 p.Val127Ile

c.379G>A · rs149201422 · VCV44697

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

ambiguous

0.4026 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4026	ambiguous
REVEL	0.608	indeterminate
SaProt	LLR -11.85	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,775 bp · p 0.57 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,934 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.0039% 63/1,614,114 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,705
European (non-Finnish)	0.00475%	21,072

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.Val127Ile
Coding: c.379G>A
MANE Select: NM_003476
dbSNP: rs149201422
Type: single nucleotide variant
Location: chr11:19186251 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.91 · 2 PDB
Residue 127: the lim zinc-binding 2 domain

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.Val127= Likely benign ★ 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-val127ile (accessed [today's date]).

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