Is DYSF p.Ser1997Phe (c.5990C>T) pathogenic?

DYSF p.Ser1997Phe (c.5990C>T) is classified Pathogenic in DYSF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-25). AlphaMissense: likely pathogenic (0.8814); Very rare (popmax 0.00223%, eas); Associated with Miyoshi muscular dystrophy 1.

What condition is associated with DYSF p.Ser1997Phe (c.5990C>T)?

DYSF p.Ser1997Phe (c.5990C>T) is associated with Miyoshi muscular dystrophy 1 (ClinVar).

How common is DYSF p.Ser1997Phe (c.5990C>T) in the general population?

DYSF p.Ser1997Phe (c.5990C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Miyoshi myopathy inherited?

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

What do computational predictors say about DYSF p.Ser1997Phe (c.5990C>T)?

AlphaMissense predicts likely pathogenic (score 0.8814) — an in-silico prediction, not a clinical call.

DYSF p.Ser1997Phe

c.5990C>T · rs2152967860 · VCV2675001

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8814 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Miyoshi muscular dystrophy 1

Computational evidence

Protein change
AlphaMissense	0.8814	likely pathogenic ✓ concordant with ClinVar
REVEL	0.916	moderately pathogenic-leaning
SaProt	LLR -15.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 117 kb · p 0.28 · regional, not allelic
Overall
CADD	25.7	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 S1958F vs ClinVar S1997F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Overall 6.84e-05% 1/1,461,790 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.Ser1997Phe
Coding: c.5990C>T
MANE Select: NM_001130987
dbSNP: rs2152967860
Type: single nucleotide variant
Location: chr2:71679162 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1997: the 'disordered' region; a β-strand

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

Disease context

Miyoshi muscular dystrophy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Miyoshi myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

DYSF p.Ser1997Cys Uncertain significance ★ ⚠ same residue
DYSF p.Ser1997= 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.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-ser1997phe (accessed [today's date]).

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