Is FLNB p.Lys712= (c.2136G>A) pathogenic?

FLNB p.Lys712= (c.2136G>A) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-01). Ultra-rare (popmax 0.0245%, eas); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Lys712= (c.2136G>A)?

FLNB p.Lys712= (c.2136G>A) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Lys712= (c.2136G>A) in the general population?

FLNB p.Lys712= (c.2136G>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

FLNB p.Lys712=

c.2136G>A · rs777288340 · VCV346320

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Conditions

FLNB-Related Spectrum Disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.78	GERP -4.2, phastCons 1
Overall
CADD	5.886	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,876 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000991% 16/1,614,244 alleles · ultra-rare exomes 13/1,461,878 · genomes 3/152,366 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,080
European (non-Finnish)	0.000424%	236,009

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.Lys712=
Coding: c.2136G>A
MANE Select: NM_001457
dbSNP: rs777288340
Type: single nucleotide variant
Location: chr3:58109259 (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

Disease context

FLNB-Related Spectrum Disorders

Similar variants

FLNB p.Glu1661Lys Uncertain significance ★★ ⚠ same condition
FLNB p.Glu78Gly Uncertain significance ★★ ⚠ same condition
FLNB p.His1117Arg Uncertain significance ★★ ⚠ same condition
FLNB p.Leu1440Pro Uncertain significance ★★ ⚠ same condition
FLNB p.Pro396Ser Uncertain significance ★★ ⚠ same condition
FLNB p.Ser1096Phe Uncertain significance ★★ ⚠ same condition
FLNB p.Ser188Cys Uncertain significance ★★ ⚠ same condition
FLNB p.Tyr63His Uncertain significance ★★ ⚠ 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/flnb-p-lys712 (accessed [today's date]).

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