Is PLEC p.Arg690fs (c.2069_2073del) pathogenic?

PLEC p.Arg690fs (c.20692073del) is classified Pathogenic in PLEC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). No gnomAD frequency available for this variant; Associated with epidermolysis bullosa simplex with nail dystrophy.

What condition is associated with PLEC p.Arg690fs (c.2069_2073del)?

PLEC p.Arg690fs (c.2069_2073del) is associated with epidermolysis bullosa simplex with nail dystrophy, epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 5B, with muscular dystrophy (ClinVar).

How common is PLEC p.Arg690fs (c.2069_2073del) in the general population?

PLEC p.Arg690fs (c.2069_2073del) is no gnomAD frequency available for this variant (gnomAD).

PLEC p.Arg690fs

c.2069_2073del · rs2538776350 · VCV2941131

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 with nail dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	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.Arg690fs
Coding: c.2069_2073del
MANE Select: NM_201384
dbSNP: rs2538776350
Type: Microsatellite
Location: chr8:143932139 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 690: an α-helix; the 'globular 1' region

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

Disease context

epidermolysis bullosa simplex with nail dystrophy — 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 autosomal recessive limb-girdle muscular dystrophy type 2Q

Similar variants

PLEC p.Arg690Trp Uncertain significance ★★ same residue
PLEC p.Arg690Gln Uncertain significance ★ same residue
PLEC p.Arg690Gly Uncertain significance ★ same residue
PLEC p.Arg690Leu Uncertain significance ★ same residue
PLEC p.Arg690Pro Uncertain significance ★ same residue
PLEC p.1943EL[2] Uncertain significance ★★ same condition
PLEC p.Gln2968_Lys2969insGluGln Uncertain significance ★★ same condition
PLEC p.Glu1668del 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-arg690fs (accessed [today's date]).

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