Is DYSF p.Arg600Gln (c.1799G>A) pathogenic?

DYSF p.Arg600Gln (c.1799G>A) is classified Likely benign in DYSF (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.1291); Ultra-rare (popmax 0.0203%, sas); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Arg600Gln (c.1799G>A) in the general population?

DYSF p.Arg600Gln (c.1799G>A) is ultra-rare (popmax 0.0203%, sas) (gnomAD).

What do computational predictors say about DYSF p.Arg600Gln (c.1799G>A)?

AlphaMissense predicts likely benign (score 0.1291) — an in-silico prediction, not a clinical call.

DYSF p.Arg600Gln

Q: What condition is associated with DYSF p.Arg600Gln (c.1799G>A)?

DYSF p.Arg600Gln (c.1799G>A) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin, autosomal recessive limb-girdle muscular dystrophy type 2B (ClinVar).

c.1799G>A · rs546679270 · VCV862087

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1291 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0203%, sas)

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	0.1291	likely benign
REVEL	0.398	indeterminate
SaProt	LLR -4.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.46	donor gain, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 85 kb · p 0.54 · regional, not allelic
Overall
CADD	34.0	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 R582Q vs ClinVar R600Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0203% South Asian · 18/88,726 alleles

Filtering AF 0.013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.0028% 45/1,604,684 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0203%	4,929
Admixed American	0.00344%	29,075
African / African-American	0.00267%	37,503
European (non-Finnish)	0.00187%	53,511
Remaining individualsnot grpmax-eligible	0.00161%	62,274

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.Arg600Gln
Coding: c.1799G>A
MANE Select: NM_001130987
dbSNP: rs546679270
Type: single nucleotide variant
Location: chr2:71551713 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 600: 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.Arg600Leu Benign ★★★ same residue
DYSF p.Arg600Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
DYSF p.Arg600= 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

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-arg600gln (accessed [today's date]).

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