Is CFL2 p.Asp66= (c.198C>T) pathogenic?

CFL2 p.Asp66= (c.198C>T) is classified Likely benign in CFL2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-11). Rare (popmax 0.345%, eas); Associated with nemaline myopathy 7.

What condition is associated with CFL2 p.Asp66= (c.198C>T)?

CFL2 p.Asp66= (c.198C>T) is associated with nemaline myopathy 7 (ClinVar).

How common is CFL2 p.Asp66= (c.198C>T) in the general population?

CFL2 p.Asp66= (c.198C>T) is rare (popmax 0.345%, eas) (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.Asp66=

c.198C>T · rs75685384 · VCV390792

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.345%, eas)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Overall
CADD	13.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.345% East Asian · 155/44,866 alleles

Filtering AF 0.301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.284%

Overall 0.01% 162/1,613,830 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.345%	289
Remaining individualsnot grpmax-eligible	0.0032%	31,250
Admixed American	0.00167%	60,000
South Asian	0.0011%	91,062
European (non-Finnish)	0.000254%	393,269

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.Asp66=
Coding: c.198C>T
MANE Select: NM_138638
dbSNP: rs75685384
Type: single nucleotide variant
Location: chr14:34713367 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 88.78 · 11 PDB
Residue 66: 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 c.4-172C>T Uncertain significance ★★ same condition
CFL2 c.*1507C>T Uncertain significance ★★ same condition
CFL2 c.*1759A>G Uncertain significance ★★ same condition
CFL2 p.Leu153Val Uncertain significance ★★ ⚠ same condition
CFL2 p.Lys31Asn Uncertain significance ★★ ⚠ same condition
CFL2 p.Met18Ile Uncertain significance ★★ ⚠ same condition
CFL2 p.Thr25Ala Uncertain significance ★★ ⚠ same condition
CFL2 p.Val57Met 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-asp66 (accessed [today's date]).

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