Is CFL2 p.Ser113fs (c.338del) pathogenic?

CFL2 p.Ser113fs (c.338del) is classified Pathogenic in CFL2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-26). Absent from gnomAD; Associated with nemaline myopathy 7.

What condition is associated with CFL2 p.Ser113fs (c.338del)?

CFL2 p.Ser113fs (c.338del) is associated with nemaline myopathy 7 (ClinVar).

How common is CFL2 p.Ser113fs (c.338del) in the general population?

CFL2 p.Ser113fs (c.338del) is absent from gnomAD (gnomAD).

How is Typical nemaline myopathy inherited?

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

CFL2 p.Ser113fs

c.338del · rs1594784544 · VCV800930

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

nemaline myopathy 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (3 of 4, 50 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFL2
Protein: p.Ser113fs
Coding: c.338del
MANE Select: NM_138638
dbSNP: rs1594784544
Type: Deletion
Location: chr14:34713110 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 88.78 · 11 PDB
Residue 113: the adf-h domain; an α-helix

Full CFL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nemaline myopathy 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Typical nemaline myopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CFL2 c.312-7del Benign ★★ same condition
CFL2 p.Ala52fs Pathogenic ★ same condition
CFL2 p.Glu28del Uncertain significance ★ same condition
CFL2 p.Tyr117fs Uncertain significance ★ same condition
CFL2 c.312-8_312-7del Benign ★ same condition
CFL2 c.389-8del Likely benign ★ same condition
CFL2 c.389-9del Likely benign ★ same condition
CFL2 p.Lys34fs 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/cfl2-p-ser113fs (accessed [today's date]).

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