Is FLNA p.Pro281fs (c.842del) pathogenic?

FLNA p.Pro281fs (c.842del) is classified Likely pathogenic in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-28). Associated with FLNA-related disorder.

What condition is associated with FLNA p.Pro281fs (c.842del)?

FLNA p.Pro281fs (c.842del) is associated with FLNA-related disorder (ClinVar).

FLNA p.Pro281fs

c.842del · VCV4953650

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

FLNA-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -20	GERP -3.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: FLNA
Protein: p.Pro281fs
Coding: c.842del
MANE Select: NM_001110556
Type: Deletion
Location: chrX:154367423 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 281: the 'disordered' region

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

Disease context

FLNA-related disorder

Similar variants

FLNA p.Arg674fs Pathogenic ★★ same condition
FLNA p.Val1721fs Pathogenic ★★ same condition
FLNA p.Pro281Ala Uncertain significance ★★ ⚠ same residue
FLNA p.Pro281Leu Uncertain significance ★★ ⚠ same residue
FLNA p.Pro281= Likely benign ★★ same residue
FLNA c.4143-6_4160del Likely pathogenic ★ same condition
FLNA c.6502+3_6502+30del Likely pathogenic ★ same condition
FLNA c.6905_6907+4del Likely pathogenic ★ 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/flna-p-pro281fs (accessed [today's date]).

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