Is DYSF p.Phe1670= (c.5010C>T) pathogenic?

DYSF p.Phe1670= (c.5010C>T) is classified Conflicting classifications of pathogenicity in DYSF (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-17). Ultra-rare (popmax 0.0271%, nfe); Associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin.

How common is DYSF p.Phe1670= (c.5010C>T) in the general population?

DYSF p.Phe1670= (c.5010C>T) is ultra-rare (popmax 0.0271%, nfe) (gnomAD).

DYSF p.Phe1670=

Q: What condition is associated with DYSF p.Phe1670= (c.5010C>T)?

DYSF p.Phe1670= (c.5010C>T) is associated with neuromuscular disease caused by qualitative or quantitative defects of dysferlin, autosomal recessive limb-girdle muscular dystrophy type 2B (ClinVar).

c.5010C>T · rs151276652 · VCV197521

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0271%, 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 -4	GERP -3.6
Overall
CADD	7.534	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0271% European (non-Finnish) · 320/1,179,992 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0237%

Overall 0.0219% 353/1,613,918 alleles · ultra-rare exomes 333/1,461,772 · genomes 20/152,146 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0271%	3,687
Remaining individualsnot grpmax-eligible	0.024%	4,165
Finnishnot grpmax-eligible	0.0219%	4,573
African / African-American	0.004%	24,973
East Asian	0.00223%	44,876

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.Phe1670=
Coding: c.5010C>T
MANE Select: NM_001130987
dbSNP: rs151276652
Type: single nucleotide variant
Location: chr2:71664274 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25 · 11 PDB
Residue 1670: an α-helix; the c2 6 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

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2B

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+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-phe1670 (accessed [today's date]).

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