Is PLEC p.Arg1685fs (c.5053del) pathogenic?

PLEC p.Arg1685fs (c.5053del) is classified Likely pathogenic in PLEC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). No gnomAD frequency available for this variant.

How common is PLEC p.Arg1685fs (c.5053del) in the general population?

PLEC p.Arg1685fs (c.5053del) is no gnomAD frequency available for this variant (gnomAD).

PLEC p.Arg1685fs

c.5053del · rs1057519155 · VCV374566

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 31 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	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.Arg1685fs
Coding: c.5053del
MANE Select: NM_201384
dbSNP: rs1057519155
Type: Deletion
Location: chr8:143924876 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 1685: 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

Similar variants

PLEC p.Arg1685Gln Uncertain significance ★★ ⚠ same residue
PLEC p.Arg1685Trp Uncertain significance ★★ same residue
PLEC p.Arg1685= Likely benign ★ same residue
PLEC p.Asn489fs Pathogenic ★★ same type
PLEC p.Glu3188fs Pathogenic ★★ same type
PLEC p.Ala4499_Arg4502del Uncertain significance ★★ same type
PLEC p.Glu4123del Uncertain significance ★★ same type
PLEC p.Ser2284_Leu2293del Uncertain significance ★★ same type

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-arg1685fs (accessed [today's date]).

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