Is DYSF p.Pro828= (c.2484C>T) pathogenic?

DYSF p.Pro828= (c.2484C>T) is classified Likely benign in DYSF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Very rare (popmax 0.00975%, nfe); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Pro828= (c.2484C>T) in the general population?

DYSF p.Pro828= (c.2484C>T) is very rare (popmax 0.00975%, nfe) (gnomAD).

DYSF p.Pro828=

Q: What condition is associated with DYSF p.Pro828= (c.2484C>T)?

DYSF p.Pro828= (c.2484C>T) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.2484C>T · rs143667543 · VCV510635

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00975%, nfe)

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 -4.5
Overall
CADD	1.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00975% European (non-Finnish) · 115/1,180,056 alleles

Filtering AF 0.00826% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00774%

Overall 0.0104% 168/1,614,152 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0468%	2,135
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,692
European (non-Finnish)grpmax	0.00975%	10,261
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.00333%	30,009
South Asian	0.00329%	30,365
African / African-American	0.00267%	37,474

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro828=
Coding: c.2484C>T
MANE Select: NM_001130987
dbSNP: rs143667543
Type: single nucleotide variant
Location: chr2:71564132 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 828: a turn

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.Pro828Ser Uncertain significance ★★ ⚠ same residue
DYSF p.Pro828Thr 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+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-pro828 (accessed [today's date]).

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