Is DYSF p.Arg1568Gln (c.4703G>A) pathogenic?

DYSF p.Arg1568Gln (c.4703G>A) is classified Likely benign in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-10). AlphaMissense: ambiguous (0.5118); Ultra-rare (popmax 0.034%, sas); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Arg1568Gln (c.4703G>A) in the general population?

DYSF p.Arg1568Gln (c.4703G>A) is ultra-rare (popmax 0.034%, sas) (gnomAD).

What do computational predictors say about DYSF p.Arg1568Gln (c.4703G>A)?

AlphaMissense predicts ambiguous (score 0.5118) — an in-silico prediction, not a clinical call.

DYSF p.Arg1568Gln

Q: What condition is associated with DYSF p.Arg1568Gln (c.4703G>A)?

DYSF p.Arg1568Gln (c.4703G>A) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.4703G>A · rs191383034 · VCV2171184

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5118 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, sas)

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

Computational evidence

Protein change
AlphaMissense	0.5118	ambiguous
REVEL	0.555	indeterminate
SaProt	LLR -8.17	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	26.4	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 R1529Q vs ClinVar R1568Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.034% South Asian · 31/91,084 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00273% 44/1,614,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.034%	2,938
Remaining individualsnot grpmax-eligible	0.008%	12,502
East Asian	0.00223%	44,884
Admixed American	0.00167%	60,024
European (non-Finnish)	0.000508%	196,672

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.Arg1568Gln
Coding: c.4703G>A
MANE Select: NM_001130987
dbSNP: rs191383034
Type: single nucleotide variant
Location: chr2:71656238 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1568: the c2 6 domain

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

Similar variants

DYSF p.Arg1568Trp Uncertain significance ★★ ⚠ same residue
DYSF p.Arg1568= Likely benign ★ 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+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-arg1568gln (accessed [today's date]).

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