Is LAMA2 p.Pro77= (c.231T>C) pathogenic?

LAMA2 p.Pro77= (c.231T>C) is classified Likely benign in LAMA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). Very rare (popmax 0.000169%, nfe); Associated with LAMA2-related muscular dystrophy.

What condition is associated with LAMA2 p.Pro77= (c.231T>C)?

LAMA2 p.Pro77= (c.231T>C) is associated with LAMA2-related muscular dystrophy (ClinVar).

How common is LAMA2 p.Pro77= (c.231T>C) in the general population?

LAMA2 p.Pro77= (c.231T>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

LAMA2 p.Pro77=

c.231T>C · rs1352441896 · VCV2860810

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

LAMA2-related muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.6	GERP -3.8
Overall
CADD	0.532	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,042 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,052 alleles · very rare exomes 0/1,461,884 · genomes 2/152,168 · joint denominator

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.Pro77=
Coding: c.231T>C
MANE Select: NM_000426
dbSNP: rs1352441896
Type: single nucleotide variant
Location: chr6:129050036 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 77: the laminin n-terminal 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.Pro77Leu 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
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-pro77 (accessed [today's date]).

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