Is PLEC p.Asp267= (c.801C>T) pathogenic?

PLEC p.Asp267= (c.801C>T) is classified Benign/Likely benign in PLEC (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-10-18). Rare (popmax 0.566%, eas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2Q.

What condition is associated with PLEC p.Asp267= (c.801C>T)?

PLEC p.Asp267= (c.801C>T) 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.Asp267= (c.801C>T) in the general population?

PLEC p.Asp267= (c.801C>T) is rare (popmax 0.566%, eas) (gnomAD).

PLEC p.Asp267=

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.801C>T · rs202218097 · VCV385141

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.566%, eas)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2Q

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.76 · evaluated, not missing
Constraint at this position
Conservation	phyloP -11
Overall
CADD	0.846	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.566% East Asian · 254/44,876 alleles

Filtering AF 0.509% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.487%

Overall 0.0223% 360/1,612,758 alleles · rare exomes 313/1,460,424 · genomes 47/152,334 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.566%	177
Ashkenazi Jewishnot grpmax-eligible	0.0642%	1,558
South Asian	0.0318%	3,141
Remaining individualsnot grpmax-eligible	0.0288%	3,471
African / African-American	0.00533%	18,762
European (non-Finnish)	0.00297%	33,712
Finnishnot grpmax-eligible	0.00159%	62,760

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.Asp267=
Coding: c.801C>T
MANE Select: NM_201384
dbSNP: rs202218097
Type: single nucleotide variant
Location: chr8:143935035 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 267: the calponin-homology (ch) 1 domain; an α-helix; the 'globular 1' region; the 'actin-binding' region

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 junctional epidermolysis bullosa with pyloric atresia 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.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
PLEC p.Gln1591Ter Pathogenic/Likely 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-asp267 (accessed [today's date]).

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