Is LAMA2 p.Pro1111= (c.3333T>A) pathogenic?

LAMA2 p.Pro1111= (c.3333T>A) is classified Uncertain significance in LAMA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0958%, eas); Associated with Congenital muscular dystrophy due to partial LAMA2 deficiency.

What condition is associated with LAMA2 p.Pro1111= (c.3333T>A)?

LAMA2 p.Pro1111= (c.3333T>A) is associated with Congenital muscular dystrophy due to partial LAMA2 deficiency (ClinVar).

How common is LAMA2 p.Pro1111= (c.3333T>A) in the general population?

LAMA2 p.Pro1111= (c.3333T>A) is ultra-rare (popmax 0.0958%, eas) (gnomAD).

LAMA2 p.Pro1111=

c.3333T>A · rs1257217941 · VCV905361

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0958%, eas)

Conditions

Congenital muscular dystrophy due to partial LAMA2 deficiency

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 -5.4	GERP -3.8
Overall
CADD	0.063	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0958% East Asian · 43/44,900 alleles

Filtering AF 0.073% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.065%

Overall 0.00266% 43/1,614,070 alleles · ultra-rare exomes 42/1,461,870 · genomes 1/152,200 · 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.Pro1111=
Coding: c.3333T>A
MANE Select: NM_000426
dbSNP: rs1257217941
Type: single nucleotide variant
Location: chr6:129313019 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1111: a UniProt-annotated variant site (in mdc1a); a UniProt-annotated variant site (in lgmdr23); the laminin egf-like 13 domain

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

Disease context

Congenital muscular dystrophy due to partial LAMA2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMA2 c.5072-3C>A Uncertain significance ★★ same condition
LAMA2 p.Ala1945Thr Uncertain significance ★★ same condition
LAMA2 p.Ala679Gly Uncertain significance ★★ ⚠ same condition
LAMA2 p.Arg1029Gln Uncertain significance ★★ ⚠ same condition
LAMA2 p.Arg1102Cys Uncertain significance ★★ ⚠ same condition
LAMA2 p.Arg896Trp Uncertain significance ★★ ⚠ same condition
LAMA2 p.Asn1597Ile Uncertain significance ★★ same condition
LAMA2 p.Asn2045Asp 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/lama2-p-pro1111 (accessed [today's date]).

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