Is DYSF p.Ser1875= (c.5625C>T) pathogenic?

DYSF p.Ser1875= (c.5625C>T) is classified Conflicting classifications of pathogenicity in DYSF (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-19). Rare (popmax 0.186%, sas); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Ser1875= (c.5625C>T) in the general population?

DYSF p.Ser1875= (c.5625C>T) is rare (popmax 0.186%, sas) (gnomAD).

DYSF p.Ser1875=

Q: What condition is associated with DYSF p.Ser1875= (c.5625C>T)?

DYSF p.Ser1875= (c.5625C>T) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin, autosomal recessive limb-girdle muscular dystrophy type 2B (ClinVar).

c.5625C>T · rs577921112 · VCV289761

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.186%, sas)

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	donor loss, 17 bp away · masked 0 · deltas
Pangolin	Δ0.25	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -6.8	GERP -4.3
Overall
CADD	5.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.186% South Asian · 166/89,456 alleles

Filtering AF 0.162% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.0124% 199/1,608,544 alleles · rare exomes 187/1,456,274 · genomes 12/152,270 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.186%	539
Remaining individualsnot grpmax-eligible	0.016%	6,237
Finnishnot grpmax-eligible	0.00314%	31,850
East Asian	0.00223%	44,806
European (non-Finnish)	0.0017%	58,874

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.Ser1875=
Coding: c.5625C>T
MANE Select: NM_001130987
dbSNP: rs577921112
Type: single nucleotide variant
Location: chr2:71669190 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1875: the c2 7 domain; a β-strand

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

Disease context

neuromuscular disease caused by qualitative or quantitative defects of dysferlin — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2B

Similar variants

DYSF p.Ser1875Asn 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
DYSF c.1276+5G>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-ser1875 (accessed [today's date]).

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