Is CFL2 p.Val159Ile (c.475G>A) pathogenic?

CFL2 p.Val159Ile (c.475G>A) is classified Uncertain significance in CFL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: likely benign (0.0681); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CFL2 p.Val159Ile (c.475G>A)?

CFL2 p.Val159Ile (c.475G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFL2 p.Val159Ile (c.475G>A) in the general population?

CFL2 p.Val159Ile (c.475G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFL2 p.Val159Ile (c.475G>A)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

CFL2 p.Val159Ile

c.475G>A · rs1885356615 · VCV2339192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -7.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 1,672 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	21.0	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.Val159Ile
Coding: c.475G>A
MANE Select: NM_138638
dbSNP: rs1885356615
Type: single nucleotide variant
Location: chr14:34712891 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 88.78 · 11 PDB
Residue 159: a β-strand

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.Val159Phe Uncertain significance ★ 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.Ser147Leu Uncertain significance ★ ⚠ same condition
CFL2 p.Val159del Uncertain significance ★ same residue

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-val159ile (accessed [today's date]).

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