Is DYSF p.Ile635= (c.1905C>T) pathogenic?

DYSF p.Ile635= (c.1905C>T) is classified Benign/Likely benign in DYSF (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). Rare (popmax 0.455%, sas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2B.

What condition is associated with DYSF p.Ile635= (c.1905C>T)?

DYSF p.Ile635= (c.1905C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2B, distal myopathy with anterior tibial onset, neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

How common is DYSF p.Ile635= (c.1905C>T) in the general population?

DYSF p.Ile635= (c.1905C>T) is rare (popmax 0.455%, sas) (gnomAD).

DYSF p.Ile635=

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.1905C>T · rs567956595 · VCV767357

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.455%, sas)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2B

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 -5.7	GERP -4.4
Overall
CADD	6.328	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.455% South Asian · 414/91,088 alleles

Filtering AF 0.418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.404%

Overall 0.0297% 480/1,614,186 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.455%	220
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0288%	3,473
East Asian	0.0267%	3,740
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,935
Finnishnot grpmax-eligible	0.00781%	12,800
Admixed American	0.00333%	30,013
European (non-Finnish)	0.00178%	56,193

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.Ile635=
Coding: c.1905C>T
MANE Select: NM_001130987
dbSNP: rs567956595
Type: single nucleotide variant
Location: chr2:71553109 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 635: an α-helix

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: distal myopathy with anterior tibial onset neuromuscular disease caused by qualitative or quantitative defects of dysferlin Miyoshi muscular dystrophy 1

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.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
DYSF c.1276+5G>C 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-ile635 (accessed [today's date]).

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