Is FLNA p.Arg674fs (c.2020_2021del) pathogenic?

FLNA p.Arg674fs (c.20202021del) is classified Pathogenic in FLNA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-22). No gnomAD frequency available for this variant; Associated with FLNA related lung disease.

What condition is associated with FLNA p.Arg674fs (c.2020_2021del)?

FLNA p.Arg674fs (c.2020_2021del) is associated with FLNA related lung disease, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Arg674fs (c.2020_2021del) in the general population?

FLNA p.Arg674fs (c.2020_2021del) is no gnomAD frequency available for this variant (gnomAD).

FLNA p.Arg674fs

c.2020_2021del · rs1569551783 · VCV623183

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

FLNA related lung disease

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 13 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP -0.43, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FLNA
Protein: p.Arg674fs
Coding: c.2020_2021del
MANE Select: NM_001110556
dbSNP: rs1569551783
Type: Deletion
Location: chrX:154364527 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 674: an α-helix

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

Disease context

FLNA related lung disease

Also linked: heterotopia, periventricular, X-linked dominant otopalatodigital syndrome type 2 Melnick-Needles syndrome frontometaphyseal dysplasia

Similar variants

FLNA p.Arg674Gly Uncertain significance ★ ⚠ same residue
FLNA p.Gln378fs Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Ter2648SerextTer? Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Val1721fs Pathogenic ★★ same condition
FLNA p.Val2212fs Pathogenic ★★ same condition
FLNA p.Lys531del Uncertain significance ★★ same condition
FLNA p.Ser1747_Pro1750del Uncertain significance ★★ same condition
FLNA c.1065+15del Likely benign ★★ 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-arg674fs (accessed [today's date]).

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