Is PLEC p.Phe307= (c.921C>T) pathogenic?

PLEC p.Phe307= (c.921C>T) is classified Benign/Likely benign in PLEC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-23). Rare (popmax 0.349%, sas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2Q.

What condition is associated with PLEC p.Phe307= (c.921C>T)?

PLEC p.Phe307= (c.921C>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.Phe307= (c.921C>T) in the general population?

PLEC p.Phe307= (c.921C>T) is rare (popmax 0.349%, sas) (gnomAD).

PLEC p.Phe307=

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.921C>T · rs546380802 · VCV283404

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.349%, sas)

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>T here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	phastCons 1
Overall
CADD	10.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.349% South Asian · 318/91,078 alleles

Filtering AF 0.318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.305%

Overall 0.0208% 336/1,611,578 alleles · rare exomes 316/1,459,240 · genomes 20/152,338 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.349%	286
Remaining individualsnot grpmax-eligible	0.0128%	7,807
Admixed American	0.01%	9,999
East Asian	0.00223%	44,884
African / African-American	0.00133%	75,054
European (non-Finnish)	0.00017%	589,908

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.Phe307=
Coding: c.921C>T
MANE Select: NM_201384
dbSNP: rs546380802
Type: single nucleotide variant
Location: chr8:143934834 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Residue 307: an α-helix; the calponin-homology (ch) 2 domain; 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 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-phe307 (accessed [today's date]).

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