Is PLEC p.Glu949= (c.2847G>A) pathogenic?

PLEC p.Glu949= (c.2847G>A) is classified Conflicting classifications of pathogenicity in PLEC (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-21). No allele count reported in gnomAD v4.1 (AN 1,599,920); Associated with autosomal recessive limb-girdle muscular dystrophy type 2Q.

What condition is associated with PLEC p.Glu949= (c.2847G>A)?

PLEC p.Glu949= (c.2847G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2Q, epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 5B, with muscular dystrophy (ClinVar).

How common is PLEC p.Glu949= (c.2847G>A) in the general population?

PLEC p.Glu949= (c.2847G>A) is no allele count reported in gnomAD v4.1 (AN 1,599,920) (gnomAD).

PLEC p.Glu949=

Q: How is Plectin-related limb-girdle muscular dystrophy R17 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2847G>A · rs1169421274 · VCV995211

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,920)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2Q

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 1.7	phastCons 1
Overall
CADD	7.928	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,599,920). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PLEC
Protein: p.Glu949=
Coding: c.2847G>A
MANE Select: NM_201384
dbSNP: rs1169421274
Type: single nucleotide variant
Location: chr8:143929722 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 949: the 'globular 1' region; the sh3 domain

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

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2Q — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolysis bullosa simplex 5A, Ogna type epidermolysis bullosa simplex 5B, with muscular dystrophy epidermolysis bullosa simplex 5C, with pyloric atresia epidermolysis bullosa simplex with nail dystrophy

For Plectin-related limb-girdle muscular dystrophy R17 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

PLEC p.Glu949Lys Uncertain significance ★ same residue
PLEC p.Arg1490Ter Pathogenic/Likely pathogenic ★★ same condition
PLEC p.Arg1973Trp Pathogenic ★★ ⚠ same condition
PLEC p.Arg2027Ter Pathogenic ★★ same condition
PLEC p.Arg2292Ter Pathogenic ★★ same condition
PLEC p.Arg2324Ter Pathogenic ★★ same condition
PLEC p.Arg2394Ter Pathogenic ★★ same condition
PLEC p.Arg559Ter 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/plec-p-glu949 (accessed [today's date]).

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