Is PLEC p.Gln2003= (c.6009G>A) pathogenic?

PLEC p.Gln2003= (c.6009G>A) is classified Likely benign in PLEC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-29). Ultra-rare (popmax 0.0827%, eas); Associated with epidermolysis bullosa simplex 5A, Ogna type.

What condition is associated with PLEC p.Gln2003= (c.6009G>A)?

PLEC p.Gln2003= (c.6009G>A) is associated with epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 5B, with muscular dystrophy, epidermolysis bullosa simplex 5C, with pyloric atresia (ClinVar).

How common is PLEC p.Gln2003= (c.6009G>A) in the general population?

PLEC p.Gln2003= (c.6009G>A) is ultra-rare (popmax 0.0827%, eas) (gnomAD).

PLEC p.Gln2003=

Q: How is PLEC-related intermediate epidermolysis bullosa simplex without extracutaneous involvement inherited?

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

c.6009G>A · rs782804807 · VCV1117099

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0827%, eas)

Conditions

epidermolysis bullosa simplex 5A, Ogna type

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 0.064	phastCons 0.89
Overall
CADD	0.813	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0827% East Asian · 37/44,726 alleles

Filtering AF 0.0617% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0544%

Overall 0.00395% 63/1,595,362 alleles · ultra-rare exomes 56/1,443,048 · genomes 7/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0827%	1,209
Middle Eastern	0.0172%	5,822
South Asian	0.011%	9,077
Remaining individualsnot grpmax-eligible	0.00483%	20,706
European (non-Finnish)	0.00102%	98,190

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: PLEC
Protein: p.Gln2003=
Coding: c.6009G>A
MANE Select: NM_201384
dbSNP: rs782804807
Type: single nucleotide variant
Location: chr8:143923920 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 2003: the 'required for interaction with intermediate filament proteins' region; the 'central fibrous rod domain' region

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

Disease context

epidermolysis bullosa simplex 5A, Ogna type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolysis bullosa simplex 5B, with muscular dystrophy epidermolysis bullosa simplex 5C, with pyloric atresia autosomal recessive limb-girdle muscular dystrophy type 2Q epidermolysis bullosa simplex with nail dystrophy

For PLEC-related intermediate epidermolysis bullosa simplex without extracutaneous involvement (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

PLEC p.Gln2003Arg 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-gln2003 (accessed [today's date]).

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