Is DYSF p.Arg1115Cys (c.3343C>T) pathogenic?

DYSF p.Arg1115Cys (c.3343C>T) is classified Conflicting classifications of pathogenicity in DYSF (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.3314); Rare (popmax 0.314%, eas); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Arg1115Cys (c.3343C>T) in the general population?

DYSF p.Arg1115Cys (c.3343C>T) is rare (popmax 0.314%, eas) (gnomAD).

What do computational predictors say about DYSF p.Arg1115Cys (c.3343C>T)?

AlphaMissense predicts likely benign (score 0.3314) — an in-silico prediction, not a clinical call.

DYSF p.Arg1115Cys

Q: What condition is associated with DYSF p.Arg1115Cys (c.3343C>T)?

DYSF p.Arg1115Cys (c.3343C>T) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin, autosomal recessive limb-girdle muscular dystrophy type 2B (ClinVar).

c.3343C>T · rs147483765 · VCV287474

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.3314 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.314%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Computational evidence

Protein change
AlphaMissense	0.3314	likely benign
REVEL	0.635	indeterminate
SaProt	LLR -9.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1.3, phastCons 0.98
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1097C vs ClinVar R1115C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.314% East Asian · 141/44,882 alleles

Filtering AF 0.272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.256%

Overall 0.0141% 227/1,614,116 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.314%	318
Remaining individualsnot grpmax-eligible	0.048%	2,083
Admixed American	0.0183%	5,457
African / African-American	0.0133%	7,505
European (non-Finnish)	0.00288%	34,707
South Asian	0.0011%	91,074

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.Arg1115Cys
Coding: c.3343C>T
MANE Select: NM_001130987
dbSNP: rs147483765
Type: single nucleotide variant
Location: chr2:71574312 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1115: a turn

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.Arg1115His 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-arg1115cys (accessed [today's date]).

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