Is PLEC p.Ala1772= (c.5316G>A) pathogenic?

PLEC p.Ala1772= (c.5316G>A) is classified Benign in PLEC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Common (popmax 7.66%, afr) — too common for a highly-penetrant pathogenic allele; Associated with epidermolysis bullosa simplex 5C, with pyloric atresia.

What condition is associated with PLEC p.Ala1772= (c.5316G>A)?

PLEC p.Ala1772= (c.5316G>A) is associated with epidermolysis bullosa simplex 5C, with pyloric atresia, epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 5B, with muscular dystrophy (ClinVar).

PLEC p.Ala1772=

Q: How common is PLEC p.Ala1772= (c.5316G>A) in the general population?

PLEC p.Ala1772= (c.5316G>A) is common (popmax 7.66%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.5316G>A · rs62642466 · VCV167509

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 7.66%, afr) — too common for a highly-penetrant pathogenic allele

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 -13
Overall
CADD	0.101	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.66% African / African-American · 5,618/73,386 alleles

Filtering AF 7.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.42%

Overall 0.46% 7,089/1,541,956 alleles · common exomes 3,803/1,389,810 · genomes 3,286/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.66%	13
Ashkenazi Jewishnot grpmax-eligible	0.709%	141
Admixed American	0.638%	157
Remaining individualsnot grpmax-eligible	0.623%	160
Middle Eastern	0.383%	261
European (non-Finnish)	0.0449%	2,225
South Asian	0.0224%	4,461
East Asian	0.00242%	41,254

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.Ala1772=
Coding: c.5316G>A
MANE Select: NM_201384
dbSNP: rs62642466
Type: single nucleotide variant
Location: chr8:143924613 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 1772: 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

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.Ala1772Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala1772 (accessed [today's date]).

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