Is CFL2 p.Pro110Ser (c.328C>T) pathogenic?

CFL2 p.Pro110Ser (c.328C>T) is classified Uncertain significance in CFL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-23). AlphaMissense: likely benign (0.3304); Very rare (popmax 0.00115%, sas); Associated with nemaline myopathy 7.

What condition is associated with CFL2 p.Pro110Ser (c.328C>T)?

CFL2 p.Pro110Ser (c.328C>T) is associated with nemaline myopathy 7 (ClinVar).

How common is CFL2 p.Pro110Ser (c.328C>T) in the general population?

CFL2 p.Pro110Ser (c.328C>T) is very rare (popmax 0.00115%, sas) (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.Pro110Ser (c.328C>T)?

AlphaMissense predicts likely benign (score 0.3304) — an in-silico prediction, not a clinical call.

CFL2 p.Pro110Ser

c.328C>T · rs1594784547 · VCV650607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3304 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00115%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

nemaline myopathy 7

Computational evidence

Protein change
AlphaMissense	0.3304	likely benign
REVEL	0.381	indeterminate
SaProt	LLR -10.69	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 1,672 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	21.3	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

Grpmax group 0.00115% South Asian · 1/87,090 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00021% 3/1,426,924 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00115%	87,090
European (non-Finnish)	0.000172%	580,538

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.Pro110Ser
Coding: c.328C>T
MANE Select: NM_138638
dbSNP: rs1594784547
Type: single nucleotide variant
Location: chr14:34713120 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 88.78 · 11 PDB
Residue 110: the adf-h domain

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-pro110ser (accessed [today's date]).

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