Is PLEC p.Pro4407Arg (c.13220C>G) pathogenic?

PLEC p.Pro4407Arg (c.13220C>G) is classified Uncertain significance in PLEC (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-27). AlphaMissense: likely benign (0.1116); Absent from gnomAD v4.1; Associated with autosomal recessive limb-girdle muscular dystrophy type 2Q.

What condition is associated with PLEC p.Pro4407Arg (c.13220C>G)?

PLEC p.Pro4407Arg (c.13220C>G) is associated with autosomal recessive limb-girdle muscular dystrophy type 2Q, epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 5B, with muscular dystrophy (ClinVar).

How common is PLEC p.Pro4407Arg (c.13220C>G) in the general population?

PLEC p.Pro4407Arg (c.13220C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLEC p.Pro4407Arg (c.13220C>G)?

AlphaMissense predicts likely benign (score 0.1116) — an in-silico prediction, not a clinical call.

PLEC p.Pro4407Arg

Q: How is Plectin-related limb-girdle muscular dystrophy R17 inherited?

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

c.13220C>G · rs1554669693 · VCV487244

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1116 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2Q

Computational evidence

Protein change
AlphaMissense	0.1116	likely benign
REVEL	0.33	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.62, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 128 bp · p 0.0005 · regional, not allelic
Overall
CADD	19.14	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P4544R vs ClinVar P4407R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PLEC
Protein: p.Pro4407Arg
Coding: c.13220C>G
MANE Select: NM_201384
dbSNP: rs1554669693
Type: single nucleotide variant
Location: chr8:143916601 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)

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

Disease context

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

For Plectin-related limb-girdle muscular dystrophy R17 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

PLEC p.Pro4407Ala Uncertain significance ★★ ⚠ same residue
PLEC p.Pro4407Leu Uncertain significance ★ same residue
PLEC p.Pro4407Ser 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

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-pro4407arg (accessed [today's date]).

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