Is DYSF p.Arg402Gln (c.1205G>A) pathogenic?

DYSF p.Arg402Gln (c.1205G>A) is classified Conflicting classifications of pathogenicity in DYSF (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-02). AlphaMissense: likely benign (0.162); Very rare (popmax 0.00267%, afr); Associated with Miyoshi muscular dystrophy 1.

What condition is associated with DYSF p.Arg402Gln (c.1205G>A)?

DYSF p.Arg402Gln (c.1205G>A) is associated with Miyoshi muscular dystrophy 1, autosomal recessive limb-girdle muscular dystrophy type 2B, distal myopathy with anterior tibial onset (ClinVar).

How common is DYSF p.Arg402Gln (c.1205G>A) in the general population?

DYSF p.Arg402Gln (c.1205G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Miyoshi myopathy inherited?

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

What do computational predictors say about DYSF p.Arg402Gln (c.1205G>A)?

AlphaMissense predicts likely benign (score 0.162) — an in-silico prediction, not a clinical call.

DYSF p.Arg402Gln

c.1205G>A · rs375071568 · VCV1437442

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Miyoshi muscular dystrophy 1

Computational evidence

Protein change
AlphaMissense	0.162	likely benign
REVEL	0.505	indeterminate
SaProt	LLR -6.30	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 8.4	GERP 0.99, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 85 kb · p 0.54 · regional, not allelic
Overall
CADD	26.5	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 R370Q vs ClinVar R402Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,940 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,614,120 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,470
European (non-Finnish)	0.000169%	590,030

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.Arg402Gln
Coding: c.1205G>A
MANE Select: NM_001130987
dbSNP: rs375071568
Type: single nucleotide variant
Location: chr2:71526275 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 402: an α-helix; the c2 3 domain

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

Disease context

Miyoshi muscular dystrophy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2B distal myopathy with anterior tibial onset neuromuscular disease caused by qualitative or quantitative defects of dysferlin

For Miyoshi myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

DYSF p.Arg402Trp Uncertain significance ★★ ⚠ same residue
DYSF p.Arg402Gly 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

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-arg402gln (accessed [today's date]).

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