Is LAMA2 p.Pro98= (c.294G>A) pathogenic?

LAMA2 p.Pro98= (c.294G>A) is classified Likely benign in LAMA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.0206%, nfe); Associated with LAMA2-related muscular dystrophy.

What condition is associated with LAMA2 p.Pro98= (c.294G>A)?

LAMA2 p.Pro98= (c.294G>A) is associated with LAMA2-related muscular dystrophy (ClinVar).

How common is LAMA2 p.Pro98= (c.294G>A) in the general population?

LAMA2 p.Pro98= (c.294G>A) is ultra-rare (popmax 0.0206%, nfe) (gnomAD).

LAMA2 p.Pro98=

c.294G>A · rs145752259 · VCV702726

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0206%, 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 -6.7	GERP -4.1
Overall
CADD	0.394	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0206% European (non-Finnish) · 240/1,164,906 alleles

Filtering AF 0.0184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0176%

Overall 0.016% 256/1,597,382 alleles · ultra-rare exomes 239/1,445,172 · genomes 17/152,210 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0206%	4,854
Remaining individualsnot grpmax-eligible	0.0113%	8,847
East Asian	0.00894%	11,181
South Asian	0.00331%	30,241
African / African-American	0.00268%	37,336

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.Pro98=
Coding: c.294G>A
MANE Select: NM_000426
dbSNP: rs145752259
Type: single nucleotide variant
Location: chr6:129059794 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 98: a UniProt-annotated variant site (in mdc1a); 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.Pro98Ala 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-pro98 (accessed [today's date]).

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