Is LAMA2 p.Pro579= (c.1737G>A) pathogenic?

LAMA2 p.Pro579= (c.1737G>A) is classified Likely benign in LAMA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-15). Ultra-rare (popmax 0.01%, amr); Associated with LAMA2-related muscular dystrophy.

What condition is associated with LAMA2 p.Pro579= (c.1737G>A)?

LAMA2 p.Pro579= (c.1737G>A) is associated with LAMA2-related muscular dystrophy (ClinVar).

How common is LAMA2 p.Pro579= (c.1737G>A) in the general population?

LAMA2 p.Pro579= (c.1737G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

LAMA2 p.Pro579=

c.1737G>A · rs149000261 · VCV772540

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Conditions

LAMA2-related muscular dystrophy

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 -8.9	GERP -3.9
Overall
CADD	0.351	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,998 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000496% 8/1,614,044 alleles · ultra-rare exomes 5/1,461,864 · genomes 3/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	8.47e-05%	1,180,032

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: LAMA2
Protein: p.Pro579=
Coding: c.1737G>A
MANE Select: NM_000426
dbSNP: rs149000261
Type: single nucleotide variant
Location: chr6:129192808 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 579: a UniProt-annotated variant site (in mdc1a); a UniProt-annotated variant site (in lgmdr23); the laminin iv type a 1 domain

Full LAMA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

LAMA2-related muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMA2 p.Pro579Leu Uncertain significance ★ ⚠ same residue
LAMA2 p.Pro579Gln Uncertain significance ★ ⚠ same residue
LAMA2 c.1028-1G>A Likely pathogenic ★★ same condition
LAMA2 c.112+1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMA2 c.112+2T>C Pathogenic ★★ same condition
LAMA2 c.1467+1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMA2 c.1467+2T>C Pathogenic/Likely pathogenic ★★ same condition
LAMA2 c.1884+1G>A Pathogenic/Likely pathogenic ★★ 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/lama2-p-pro579 (accessed [today's date]).

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