Is CFL2 p.Ser147Leu (c.440C>T) pathogenic?

CFL2 p.Ser147Leu (c.440C>T) is classified Uncertain significance in CFL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.106); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CFL2 p.Ser147Leu (c.440C>T)?

CFL2 p.Ser147Leu (c.440C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFL2 p.Ser147Leu (c.440C>T) in the general population?

CFL2 p.Ser147Leu (c.440C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFL2 p.Ser147Leu (c.440C>T)?

AlphaMissense predicts likely benign (score 0.106) — an in-silico prediction, not a clinical call.

CFL2 p.Ser147Leu

c.440C>T · rs757526740 · VCV2254241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.106 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.106	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 1,672 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Ser147Leu
Coding: c.440C>T
MANE Select: NM_138638
dbSNP: rs757526740
Type: single nucleotide variant
Location: chr14:34712926 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 88.78 · 11 PDB
Residue 147: the adf-h domain; an α-helix

Full CFL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFL2 p.Ser147= Likely benign ★★ same residue
CFL2 p.Lys31Asn Uncertain significance ★★ ⚠ same condition
CFL2 p.Ser94Phe Uncertain significance ★★ ⚠ same condition
CFL2 p.Thr25Ile Uncertain significance ★★ ⚠ same condition
CFL2 p.Asp42Asn Uncertain significance ★ ⚠ same condition
CFL2 p.His133Arg Uncertain significance ★ ⚠ same condition
CFL2 p.Val159Ile Uncertain significance ★ ⚠ same condition
CFL2 c.4-172C>T Uncertain significance ★★ same type

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-ser147leu (accessed [today's date]).

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