Is DYSF p.Ser879= (c.2637A>T) pathogenic?

DYSF p.Ser879= (c.2637A>T) is classified Benign/Likely benign in DYSF (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-03-15). Common (popmax 81.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with distal myopathy with anterior tibial onset.

How is Distal myopathy with anterior tibial onset inherited?

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

DYSF p.Ser879=

Q: What condition is associated with DYSF p.Ser879= (c.2637A>T)?

DYSF p.Ser879= (c.2637A>T) is associated with distal myopathy with anterior tibial onset, autosomal recessive limb-girdle muscular dystrophy type 2B, neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

Q: How common is DYSF p.Ser879= (c.2637A>T) in the general population?

DYSF p.Ser879= (c.2637A>T) is common (popmax 81.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2637A>T · rs2288355 · VCV94290

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Common

common (popmax 81.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

distal myopathy with anterior tibial onset

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 -2.3	GERP -4.3
Overall
CADD	6.472	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 81.6% African / African-American · 61,152/74,952 alleles

Filtering AF 81% ClinGen BA1/BS1 input FAF95, joint · FAF99 80.8%

Overall 65.5% 1,056,348/1,613,856 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	81.6%	1
European (non-Finnish)	68.3%	1
Finnishnot grpmax-eligible	65.1%	2
Ashkenazi Jewishnot grpmax-eligible	64.3%	2
Remaining individualsnot grpmax-eligible	63%	2
Amishnot grpmax-eligible	62.4%	2
Middle Eastern	59.1%	2
Admixed American	55.3%	2
South Asian	48.6%	2
East Asian	17.9%	6

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.Ser879=
Coding: c.2637A>T
MANE Select: NM_001130987
dbSNP: rs2288355
Type: single nucleotide variant
Location: chr2:71568022 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 879: a β-strand

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

Disease context

distal myopathy with anterior tibial onset — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2B neuromuscular disease caused by qualitative or quantitative defects of dysferlin Miyoshi muscular dystrophy 1

For Distal myopathy with anterior tibial onset (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult

Similar variants

DYSF p.Ser879Ala Uncertain significance ★ ⚠ same residue
DYSF p.Ser879Ter Likely pathogenic ★ 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-ser879 (accessed [today's date]).

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