Is DYSF p.Phe440= (c.1320C>T) pathogenic?

DYSF p.Phe440= (c.1320C>T) is classified Likely benign in DYSF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-30). Ultra-rare (popmax 0.0439%, sas); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Phe440= (c.1320C>T) in the general population?

DYSF p.Phe440= (c.1320C>T) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

DYSF p.Phe440=

Q: What condition is associated with DYSF p.Phe440= (c.1320C>T)?

DYSF p.Phe440= (c.1320C>T) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin (ClinVar).

c.1320C>T · rs779669549 · VCV390830

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, 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	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.48	GERP -3.8, phastCons 1
Overall
CADD	12.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0439% South Asian · 40/91,052 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00446% 72/1,614,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,276
Remaining individualsnot grpmax-eligible	0.0064%	15,628
African / African-American	0.00533%	18,762
East Asian	0.00446%	22,439
European (non-Finnish)	0.00186%	53,637

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.Phe440=
Coding: c.1320C>T
MANE Select: NM_001130987
dbSNP: rs779669549
Type: single nucleotide variant
Location: chr2:71528341 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 440: the c2 3 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 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
DYSF c.1481-1G>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-phe440 (accessed [today's date]).

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