Is DYSF p.Pro1007Thr (c.3019C>A) pathogenic?

DYSF p.Pro1007Thr (c.3019C>A) is classified Uncertain significance in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-22). AlphaMissense: ambiguous (0.422); Very rare (popmax 8.47e-05%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2B.

What condition is associated with DYSF p.Pro1007Thr (c.3019C>A)?

DYSF p.Pro1007Thr (c.3019C>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2B (ClinVar).

How common is DYSF p.Pro1007Thr (c.3019C>A) in the general population?

DYSF p.Pro1007Thr (c.3019C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DYSF p.Pro1007Thr (c.3019C>A)?

AlphaMissense predicts ambiguous (score 0.422) — an in-silico prediction, not a clinical call.

DYSF p.Pro1007Thr

Q: How is Dysferlin-related limb-girdle muscular dystrophy R2 inherited?

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

c.3019C>A · VCV3362453

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.422 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2B

Computational evidence

Protein change
AlphaMissense	0.422	ambiguous
REVEL	0.833	moderately pathogenic-leaning
SaProt	LLR -10.79	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	25.1	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 P989T vs ClinVar P1007T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,018 alleles

Overall 6.84e-05% 1/1,461,878 alleles · very rare

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.Pro1007Thr
Coding: c.3019C>A
MANE Select: NM_001130987
Type: single nucleotide variant
Location: chr2:71570268 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB

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

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dysferlin-related limb-girdle muscular dystrophy R2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult
Prevalence: 1-9 / 1 000 000 (United Kingdom)

Similar variants

DYSF p.Pro1007Leu Uncertain significance ★★ ⚠ same residue
DYSF p.Pro1007= Likely benign ★ same residue
DYSF c.1033+1G>A 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
DYSF c.1276+5G>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-pro1007thr (accessed [today's date]).

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