Is CFL2 p.Ala83Val (c.248C>T) pathogenic?

CFL2 p.Ala83Val (c.248C>T) is classified Uncertain significance in CFL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-28). AlphaMissense: likely pathogenic (0.9207); Absent from gnomAD v4.1.

How common is CFL2 p.Ala83Val (c.248C>T) in the general population?

CFL2 p.Ala83Val (c.248C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFL2 p.Ala83Val (c.248C>T)?

AlphaMissense predicts likely pathogenic (score 0.9207) — an in-silico prediction, not a clinical call.

CFL2 p.Ala83Val

c.248C>T · rs1555333790 · VCV546737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9207 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9207	likely pathogenic
REVEL	0.235	benign-leaning
SaProt	LLR -10.87	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.29 · evaluated, not missing
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	25.9	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

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.Ala83Val
Coding: c.248C>T
MANE Select: NM_138638
dbSNP: rs1555333790
Type: single nucleotide variant
Location: chr14:34713317 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 88.78 · 11 PDB
Residue 83: 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

Similar variants

CFL2 c.4-172C>T Uncertain significance ★★ same type
CFL2 c.*1507C>T Uncertain significance ★★ same type
CFL2 c.*1759A>G Uncertain significance ★★ same type
CFL2 p.Leu153Val Uncertain significance ★★ ⚠ same type
CFL2 p.Lys31Asn Uncertain significance ★★ ⚠ same type
CFL2 p.Met18Ile Uncertain significance ★★ ⚠ same type
CFL2 p.Ser94Phe Uncertain significance ★★ ⚠ same type
CFL2 p.Thr25Ala 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-ala83val (accessed [today's date]).

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