Is PLEC p.Phe2945fs (c.8807_8832dup) pathogenic?

PLEC p.Phe2945fs (c.88078832dup) is classified Pathogenic in PLEC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-27). No gnomAD frequency available for this variant; Associated with epidermolysis bullosa simplex 5A, Ogna type.

What condition is associated with PLEC p.Phe2945fs (c.8807_8832dup)?

PLEC p.Phe2945fs (c.8807_8832dup) 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.Phe2945fs (c.8807_8832dup) in the general population?

PLEC p.Phe2945fs (c.8807_8832dup) is no gnomAD frequency available for this variant (gnomAD).

PLEC p.Phe2945fs

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.8807_8832dup · rs2537428279 · VCV2114563

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

epidermolysis bullosa simplex 5A, Ogna type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (32 of 32) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Phe2945fs
Coding: c.8807_8832dup
MANE Select: NM_201384
dbSNP: rs2537428279
Type: Duplication
Location: chr8:143920988 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 2945: the 'required for interaction with intermediate filament proteins' region; the 'globular 2' 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.Phe2945Leu Uncertain significance ★★ ⚠ same residue
PLEC p.Ser2696fs Pathogenic ★★ same condition
PLEC p.Arg2536_Gln2539dup Uncertain significance ★★ same condition
PLEC p.Arg3200_Asp3202dup Uncertain significance ★★ same condition
PLEC p.Pro1010_Leu1011dup Uncertain significance ★★ same condition
PLEC c.2304+9dup Benign ★★ same condition
PLEC c.945+19dup Benign/Likely benign ★★ same condition
PLEC p.Arg4310fs 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-phe2945fs (accessed [today's date]).

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