Is CFL2 p.Ser24del (c.67TCT[1]) pathogenic?

CFL2 p.Ser24del (c.67TCT[1]) is classified Uncertain significance in CFL2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-14). Very rare (popmax 0.00246%, nfe); Associated with nemaline myopathy 7.

What condition is associated with CFL2 p.Ser24del (c.67TCT[1])?

CFL2 p.Ser24del (c.67TCT[1]) is associated with nemaline myopathy 7 (ClinVar).

How common is CFL2 p.Ser24del (c.67TCT[1]) in the general population?

CFL2 p.Ser24del (c.67TCT[1]) is very rare (popmax 0.00246%, nfe) (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.Ser24del

c.67TCT[1] · rs774697837 · VCV2419864

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Conditions

nemaline myopathy 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	phastCons 1
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,179,864 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00217% 35/1,613,832 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,685
East Asian	0.00223%	44,886
South Asian	0.0022%	45,544
Admixed American	0.00167%	60,002
Finnishnot grpmax-eligible	0.00156%	64,004
African / African-American	0.00133%	74,920

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: CFL2
Protein: p.Ser24del
Coding: c.67TCT[1]
MANE Select: NM_138638
dbSNP: rs774697837
Type: Microsatellite
Location: chr14:34713493 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 88.78 · 11 PDB
Residue 24: a turn; the adf-h domain; the 'interaction with csrp3' region

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 p.Ser24Ala Uncertain significance ★ ⚠ same residue
CFL2 p.Lys34fs Pathogenic ★★ same condition
CFL2 p.Asp9del Uncertain significance ★ same condition
CFL2 p.Val159del Uncertain significance ★ same condition
CFL2 c.4-12_4-11del Likely benign ★ same condition
CFL2 c.4-172C>T Uncertain significance ★★ same condition
CFL2 c.*1507C>T Uncertain significance ★★ same condition
CFL2 c.*1759A>G Uncertain significance ★★ 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-ser24del (accessed [today's date]).

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