Is PLEC p.Pro4407Ser (c.13218_13219delinsTT) pathogenic?

PLEC p.Pro4407Ser (c.1321813219delinsTT) is classified Uncertain significance in PLEC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-17). No gnomAD frequency available for this variant; Associated with epidermolysis bullosa simplex 5B, with muscular dystrophy.

What condition is associated with PLEC p.Pro4407Ser (c.13218_13219delinsTT)?

PLEC p.Pro4407Ser (c.13218_13219delinsTT) is associated with epidermolysis bullosa simplex 5B, with muscular dystrophy, epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 5C, with pyloric atresia (ClinVar).

How common is PLEC p.Pro4407Ser (c.13218_13219delinsTT) in the general population?

PLEC p.Pro4407Ser (c.13218_13219delinsTT) is no gnomAD frequency available for this variant (gnomAD).

PLEC p.Pro4407Ser

Q: How is Epidermolysis bullosa simplex with muscular dystrophy inherited?

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

c.13218_13219delinsTT · rs2130801721 · VCV1470902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

epidermolysis bullosa simplex 5B, with muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.052	GERP -3.7, phastCons 0.15
Regional constraint	o/e 0.56	unconstrained · MANE · 128 bp · p 0.0005 · regional, not allelic

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.Pro4407Ser
Coding: c.13218_13219delinsTT
MANE Select: NM_201384
dbSNP: rs2130801721
Type: Indel
Location: chr8:143916602 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 4407: 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 5B, with muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Epidermolysis bullosa simplex with muscular dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PLEC p.Pro4407Ala Uncertain significance ★★ ⚠ same residue
PLEC p.Pro4407Arg Uncertain significance ★ same residue
PLEC p.Pro4407Leu Uncertain significance ★ same residue
PLEC p.Gln3001Ter Pathogenic/Likely pathogenic ★★ same condition
PLEC p.Ala2057Met Uncertain significance ★★ same condition
PLEC c.2457+5_2457+6delinsTT Uncertain significance ★ same condition
PLEC p.Ala2105Met Conflicting classifications of pathogenicity ★ same condition
PLEC p.Ala4508Asn 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/plec-p-pro4407ser (accessed [today's date]).

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