Is DYSF p.Lys1637= (c.4911G>A) pathogenic?

DYSF p.Lys1637= (c.4911G>A) is classified Conflicting classifications of pathogenicity in DYSF (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2024-05-22). Ultra-rare (popmax 0.0428%, sas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2B.

What condition is associated with DYSF p.Lys1637= (c.4911G>A)?

DYSF p.Lys1637= (c.4911G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2B, neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

How common is DYSF p.Lys1637= (c.4911G>A) in the general population?

DYSF p.Lys1637= (c.4911G>A) is ultra-rare (popmax 0.0428%, sas) (gnomAD).

DYSF p.Lys1637=

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.4911G>A · rs141704244 · VCV288089

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0428%, 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	Δ0.67	donor gain, 45 bp away · masked 0 · deltas
Pangolin	Δ0.49	gain · loss 0.39 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.1, phastCons 1
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0428% South Asian · 39/91,076 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.00273% 44/1,613,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0428%	2,335
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.000254%	393,343

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.Lys1637=
Coding: c.4911G>A
MANE Select: NM_001130987
dbSNP: rs141704244
Type: single nucleotide variant
Location: chr2:71659033 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1637: a β-strand; the c2 6 domain

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

Also linked: neuromuscular disease caused by qualitative or quantitative defects of dysferlin

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 p.Lys1637Ter Pathogenic ★ same residue
DYSF p.Lys1637Asn Uncertain significance ★ ⚠ same residue
DYSF c.1003-3C>A Pathogenic ★★★ same condition
DYSF c.1033+1G>A Pathogenic ★★★ same condition
DYSF c.1033+4A>T Likely 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

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-lys1637 (accessed [today's date]).

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