Is DYSF p.Thr720= (c.2160G>A) pathogenic?

DYSF p.Thr720= (c.2160G>A) is classified Likely benign in DYSF (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-01). Very rare (popmax 0.00583%, sas); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Thr720= (c.2160G>A) in the general population?

DYSF p.Thr720= (c.2160G>A) is very rare (popmax 0.00583%, sas) (gnomAD).

DYSF p.Thr720=

Q: What condition is associated with DYSF p.Thr720= (c.2160G>A)?

DYSF p.Thr720= (c.2160G>A) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin, autosomal recessive limb-girdle muscular dystrophy type 2B (ClinVar).

c.2160G>A · rs762651388 · VCV704531

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00583%, sas)

Conditions

neuromuscular disease caused by qualitative or quantitative defects of dysferlin

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 -20	GERP -2.9
Overall
CADD	0.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00583% South Asian · 5/85,758 alleles

Filtering AF 0.0022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00144%

Overall 0.00114% 18/1,578,310 alleles · very rare exomes 16/1,426,086 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00583%	17,152
African / African-American	0.00402%	24,876
European (non-Finnish)	0.00086%	116,278

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.Thr720=
Coding: c.2160G>A
MANE Select: NM_001130987
dbSNP: rs762651388
Type: single nucleotide variant
Location: chr2:71556015 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 720: an α-helix

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.Thr720Met Conflicting classifications of pathogenicity ★ ⚠ 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-thr720 (accessed [today's date]).

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