Is LAMA4 p.Ala1237= (c.3711A>G) pathogenic?

LAMA4 p.Ala1237= (c.3711A>G) is classified Likely benign in LAMA4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-15). Very rare (popmax 0.00526%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LAMA4 p.Ala1237= (c.3711A>G)?

LAMA4 p.Ala1237= (c.3711A>G) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1JJ (ClinVar).

How common is LAMA4 p.Ala1237= (c.3711A>G) in the general population?

LAMA4 p.Ala1237= (c.3711A>G) is very rare (popmax 0.00526%, nfe) (gnomAD).

LAMA4 p.Ala1237=

c.3711A>G · rs782816810 · VCV2060242

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00526%, nfe)

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 -5.4
Overall
CADD	5.765	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00526% European (non-Finnish) · 62/1,179,388 alleles

Filtering AF 0.00419% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00391% 63/1,613,032 alleles · very rare exomes 61/1,460,804 · genomes 2/152,228 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00526%	19,022
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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: LAMA4
Protein: p.Ala1237=
Coding: c.3711A>G
MANE Select: NM_001105206
dbSNP: rs782816810
Type: single nucleotide variant
Location: chr6:112132876 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.75
Residue 1237: the laminin g-like 3 domain

Full LAMA4 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 1JJ

Similar variants

LAMA4 c.1077+4C>T Uncertain significance ★★ same condition
LAMA4 c.1077+5G>A Uncertain significance ★★ same condition
LAMA4 c.1357+1G>A Uncertain significance ★★ same condition
LAMA4 c.3283-3C>G Uncertain significance ★★ same condition
LAMA4 c.3557+4A>G Uncertain significance ★★ same condition
LAMA4 c.3697-3C>T Uncertain significance ★★ same condition
LAMA4 c.4666-3C>T Uncertain significance ★★ same condition
LAMA4 c.5206+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/lama4-p-ala1237 (accessed [today's date]).

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