Is PLEC p.Ala1367= (c.4101C>T) pathogenic?

PLEC p.Ala1367= (c.4101C>T) is classified Benign/Likely benign in PLEC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-19). Rare (popmax 0.315%, afr); Associated with Inborn genetic diseases.

What condition is associated with PLEC p.Ala1367= (c.4101C>T)?

PLEC p.Ala1367= (c.4101C>T) is associated with Inborn genetic diseases, epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 5B, with muscular dystrophy (ClinVar).

How common is PLEC p.Ala1367= (c.4101C>T) in the general population?

PLEC p.Ala1367= (c.4101C>T) is rare (popmax 0.315%, afr) (gnomAD).

PLEC p.Ala1367=

c.4101C>T · rs376065732 · VCV283968

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.315%, afr)

Conditions

Inborn genetic diseases

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 -3.2
Overall
CADD	2.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.315% African / African-American · 233/74,056 alleles

Filtering AF 0.281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.269%

Overall 0.0202% 315/1,559,342 alleles · rare exomes 166/1,407,050 · genomes 149/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.315%	318
Admixed American	0.0422%	2,370
Remaining individualsnot grpmax-eligible	0.0329%	3,036
East Asian	0.00941%	10,628
Ashkenazi Jewishnot grpmax-eligible	0.00692%	14,448
South Asian	0.00346%	28,915
European (non-Finnish)	0.00259%	38,667

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.Ala1367=
Coding: c.4101C>T
MANE Select: NM_201384
dbSNP: rs376065732
Type: single nucleotide variant
Location: chr8:143925828 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 1367: 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

Inborn genetic diseases — 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 epidermolysis bullosa simplex with nail dystrophy

Similar variants

PLEC p.Ala1367Ser 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
PLEC p.Arg2394Ter Pathogenic ★★ same condition
PLEC p.Arg559Ter 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-ala1367 (accessed [today's date]).

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