Is LAMA2 p.Ala577Val (c.1730C>T) pathogenic?

LAMA2 p.Ala577Val (c.1730C>T) is classified Uncertain significance in LAMA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-13). AlphaMissense: likely benign (0.0748); Absent from gnomAD v4.1; Associated with LAMA2-related muscular dystrophy.

What condition is associated with LAMA2 p.Ala577Val (c.1730C>T)?

LAMA2 p.Ala577Val (c.1730C>T) is associated with LAMA2-related muscular dystrophy (ClinVar).

How common is LAMA2 p.Ala577Val (c.1730C>T) in the general population?

LAMA2 p.Ala577Val (c.1730C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LAMA2 p.Ala577Val (c.1730C>T)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

LAMA2 p.Ala577Val

c.1730C>T · rs2115037122 · VCV1902069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

LAMA2-related muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.49	GERP -3.9
Regional constraint	o/e 1.00	unconstrained · MANE · 351 kb · p 0.83 · regional, not allelic
Overall
CADD	0.348	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LAMA2
Protein: p.Ala577Val
Coding: c.1730C>T
MANE Select: NM_000426
dbSNP: rs2115037122
Type: single nucleotide variant
Location: chr6:129192801 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 577: 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.Ala577= Likely benign ★ 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
LAMA2 c.1884+2T>C 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-ala577val (accessed [today's date]).

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