Is FLNB p.Gln2160fs (c.6478dup) pathogenic?

FLNB p.Gln2160fs (c.6478dup) is classified Pathogenic in FLNB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). Very rare (popmax 8.47e-05%, nfe).

How common is FLNB p.Gln2160fs (c.6478dup) in the general population?

FLNB p.Gln2160fs (c.6478dup) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

FLNB p.Gln2160fs

c.6478dup · VCV3652535

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 39 of 46
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.7	GERP 0.65, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,050 alleles

Overall 6.84e-05% 1/1,461,860 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FLNB
Protein: p.Gln2160fs
Coding: c.6478dup
MANE Select: NM_001457
Type: Duplication
Location: chr3:58153481 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2160: the 'interaction with flna 1' region; the 'interaction with inppl1' region

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

Similar variants

FLNB p.Gln2160= Uncertain significance ★ same residue
FLNB p.Gln2160Pro Uncertain significance ★ ⚠ same residue
FLNB p.Ala971fs Pathogenic/Likely pathogenic ★★ same type
FLNB p.His532fs Pathogenic/Likely pathogenic ★★ same type
FLNB p.Ser581fs Pathogenic ★★ same type
FLNB p.Val1195fs Pathogenic/Likely pathogenic ★★ same type
FLNB p.Asp1781fs Likely pathogenic ★ same type
FLNB p.Glu1708fs Pathogenic ★ 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/flnb-p-gln2160fs (accessed [today's date]).

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