Is PLEC p.Arg1064= (c.3192C>T) pathogenic?

PLEC p.Arg1064= (c.3192C>T) is classified Benign in PLEC (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Low-frequency (popmax 3.82%, afr); Associated with epidermolysis bullosa simplex 5C, with pyloric atresia.

What condition is associated with PLEC p.Arg1064= (c.3192C>T)?

PLEC p.Arg1064= (c.3192C>T) is associated with epidermolysis bullosa simplex 5C, with pyloric atresia, epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 5B, with muscular dystrophy (ClinVar).

How common is PLEC p.Arg1064= (c.3192C>T) in the general population?

PLEC p.Arg1064= (c.3192C>T) is low-frequency (popmax 3.82%, afr) (gnomAD).

PLEC p.Arg1064=

Q: How is Epidermolysis bullosa simplex with pyloric atresia inherited?

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

c.3192C>T · rs73377210 · VCV129943

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.82%, afr)

Conditions

epidermolysis bullosa simplex 5C, with pyloric atresia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	phastCons 1
Overall
CADD	8.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.82% African / African-American · 2,859/74,924 alleles

Filtering AF 3.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.65%

Overall 0.198% 3,157/1,595,606 alleles · low-frequency exomes 1,615/1,443,232 · genomes 1,542/152,374 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.82%	26
Remaining individualsnot grpmax-eligible	0.231%	433
Admixed American	0.199%	503
Middle Eastern	0.0663%	1,509
South Asian	0.0079%	12,664
European (non-Finnish)	0.00256%	39,106

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PLEC
Protein: p.Arg1064=
Coding: c.3192C>T
MANE Select: NM_201384
dbSNP: rs73377210
Type: single nucleotide variant
Location: chr8:143929171 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 1064: an α-helix; the 'required for interaction with intermediate filament proteins' region; the 'globular 1' region

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

Disease context

epidermolysis bullosa simplex 5C, with pyloric atresia — 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 autosomal recessive limb-girdle muscular dystrophy type 2Q epidermolysis bullosa simplex with nail dystrophy

For Epidermolysis bullosa simplex with pyloric atresia (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

PLEC p.Arg1064Cys Uncertain significance ★★ same residue
PLEC p.Arg1064His Benign/Likely benign ★★ same residue
PLEC p.Arg1064Leu 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-arg1064 (accessed [today's date]).

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