Is DYSF p.Gly981= (c.2943C>T) pathogenic?

DYSF p.Gly981= (c.2943C>T) is classified Conflicting classifications of pathogenicity in DYSF (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-27). Very rare (popmax 0.0011%, sas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2B.

What condition is associated with DYSF p.Gly981= (c.2943C>T)?

DYSF p.Gly981= (c.2943C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2B (ClinVar).

How common is DYSF p.Gly981= (c.2943C>T) in the general population?

DYSF p.Gly981= (c.2943C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

DYSF p.Gly981=

Q: How is Dysferlin-related limb-girdle muscular dystrophy R2 inherited?

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

c.2943C>T · rs886042637 · VCV283479

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.92	donor gain, 2 bp away · masked 0 · deltas
Pangolin	Δ0.71	gain · loss 0.28 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.3	GERP 2.1, phastCons 1
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,058 alleles

Overall 0.000186% 3/1,613,978 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,482
South Asiangrpmax	0.0011%	91,058
European (non-Finnish)	8.47e-05%	1,180,020

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DYSF
Protein: p.Gly981=
Coding: c.2943C>T
MANE Select: NM_001130987
dbSNP: rs886042637
Type: single nucleotide variant
Location: chr2:71569898 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB

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

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dysferlin-related limb-girdle muscular dystrophy R2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult
Prevalence: 1-9 / 1 000 000 (United Kingdom)

Similar variants

DYSF c.1033+1G>A Pathogenic ★★★ same condition
DYSF c.1149+1G>A Pathogenic ★★★ same condition
DYSF c.1149+1G>C Pathogenic ★★★ same condition
DYSF c.1149+4A>G Pathogenic ★★★ same condition
DYSF c.1276+5G>A Pathogenic ★★★ same condition
DYSF c.1276+5G>C Pathogenic ★★★ same condition
DYSF c.1481-1G>A Pathogenic ★★★ same condition
DYSF c.1693-6T>A 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/dysf-p-gly981 (accessed [today's date]).

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