Is DYSF p.Ser143= (c.429C>T) pathogenic?

DYSF p.Ser143= (c.429C>T) is classified Benign/Likely benign in DYSF (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-24). Rare (popmax 0.588%, afr); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Ser143= (c.429C>T) in the general population?

DYSF p.Ser143= (c.429C>T) is rare (popmax 0.588%, afr) (gnomAD).

DYSF p.Ser143=

Q: What condition is associated with DYSF p.Ser143= (c.429C>T)?

DYSF p.Ser143= (c.429C>T) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.429C>T · rs115390288 · VCV284837

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.588%, afr)

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 -1.3	GERP -0.098
Overall
CADD	2.467	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.588% African / African-American · 430/73,188 alleles

Filtering AF 0.542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.524%

Overall 0.0315% 488/1,551,358 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.588%	170
South Asian	0.0298%	3,361
Remaining individualsnot grpmax-eligible	0.0283%	3,535
Admixed American	0.0274%	3,644
European (non-Finnish)	0.000174%	573,401

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.Ser143=
Coding: c.429C>T
MANE Select: NM_001130987
dbSNP: rs115390288
Type: single nucleotide variant
Location: chr2:71511890 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 143: the 'disordered' region

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.Ser143Thr 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
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-ser143 (accessed [today's date]).

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