Is FLNB p.Ser581fs (c.1740dup) pathogenic?

FLNB p.Ser581fs (c.1740dup) is classified Pathogenic in FLNB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-02). Very rare (popmax 0.00186%, nfe).

How common is FLNB p.Ser581fs (c.1740dup) in the general population?

FLNB p.Ser581fs (c.1740dup) is very rare (popmax 0.00186%, nfe) (gnomAD).

FLNB p.Ser581fs

c.1740dup · rs1000098671 · VCV1098338

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00186%, 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 11 of 46
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,179,990 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00149% 24/1,613,924 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00186%	53,636
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00134%	74,886

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.Ser581fs
Coding: c.1740dup
MANE Select: NM_001457
dbSNP: rs1000098671
Type: Duplication
Location: chr3:58105205 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB

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

Similar variants

FLNB p.Ala971fs Pathogenic/Likely pathogenic ★★ same type
FLNB p.His532fs Pathogenic/Likely pathogenic ★★ same type
FLNB p.Val1195fs Pathogenic/Likely pathogenic ★★ same type
FLNB p.Asp1781fs Likely pathogenic ★ same type
FLNB p.Gln2160fs Pathogenic ★ same type
FLNB p.Glu1708fs Pathogenic ★ same type
FLNB p.Lys16fs Pathogenic ★ same type
FLNB p.Lys31fs 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-ser581fs (accessed [today's date]).

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