Is CFL2 p.Arg81Gln (c.242G>A) pathogenic?

CFL2 p.Arg81Gln (c.242G>A) is classified Conflicting classifications of pathogenicity in CFL2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-01). AlphaMissense: likely pathogenic (0.9785); Absent from gnomAD v4.1; Associated with nemaline myopathy 7.

What condition is associated with CFL2 p.Arg81Gln (c.242G>A)?

CFL2 p.Arg81Gln (c.242G>A) is associated with nemaline myopathy 7, centronuclear myopathy (ClinVar).

How common is CFL2 p.Arg81Gln (c.242G>A) in the general population?

CFL2 p.Arg81Gln (c.242G>A) is absent from gnomAD v4.1 (gnomAD).

How is Typical nemaline myopathy inherited?

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

What do computational predictors say about CFL2 p.Arg81Gln (c.242G>A)?

AlphaMissense predicts likely pathogenic (score 0.9785) — an in-silico prediction, not a clinical call.

CFL2 p.Arg81Gln

c.242G>A · rs1885381246 · VCV971564

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9785 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,924)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nemaline myopathy 7

Computational evidence

Protein change
AlphaMissense	0.9785	likely pathogenic
REVEL	0.85	moderately pathogenic-leaning
SaProt	LLR -14.89	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 6	phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 1,672 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,924). 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.Arg81Gln
Coding: c.242G>A
MANE Select: NM_138638
dbSNP: rs1885381246
Type: single nucleotide variant
Location: chr14:34713323 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 88.78 · 11 PDB
Residue 81: the adf-h domain; a β-strand; 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

Also linked: centronuclear myopathy

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-arg81gln (accessed [today's date]).

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