Is CFL2 p.Gly130Arg (c.388G>C) pathogenic?

CFL2 p.Gly130Arg (c.388G>C) is classified Uncertain significance in CFL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-03). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1; Associated with nemaline myopathy 7.

What condition is associated with CFL2 p.Gly130Arg (c.388G>C)?

CFL2 p.Gly130Arg (c.388G>C) is associated with nemaline myopathy 7 (ClinVar).

How common is CFL2 p.Gly130Arg (c.388G>C) in the general population?

CFL2 p.Gly130Arg (c.388G>C) 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.Gly130Arg (c.388G>C)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

CFL2 p.Gly130Arg

c.388G>C · rs1566525113 · VCV583009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nemaline myopathy 7

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic · top 1% in CFL2
REVEL	0.878	moderately pathogenic-leaning
SaProt	LLR -16.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.99	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.88	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 1,672 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFL2
Protein: p.Gly130Arg
Coding: c.388G>C
MANE Select: NM_138638
dbSNP: rs1566525113
Type: single nucleotide variant
Location: chr14:34713060 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 88.78 · 11 PDB
Residue 130: the adf-h domain; a β-strand

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-gly130arg (accessed [today's date]).

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