Is FLNB p.Thr806Lys (c.2417C>A) pathogenic?

FLNB p.Thr806Lys (c.2417C>A) is classified Uncertain significance in FLNB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-25). AlphaMissense: likely pathogenic (0.9355); Very rare (popmax 0.00167%, amr); Associated with atelosteogenesis type III.

What condition is associated with FLNB p.Thr806Lys (c.2417C>A)?

FLNB p.Thr806Lys (c.2417C>A) is associated with atelosteogenesis type III (ClinVar).

How common is FLNB p.Thr806Lys (c.2417C>A) in the general population?

FLNB p.Thr806Lys (c.2417C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about FLNB p.Thr806Lys (c.2417C>A)?

AlphaMissense predicts likely pathogenic (score 0.9355) — an in-silico prediction, not a clinical call.

FLNB p.Thr806Lys

c.2417C>A · rs940585956 · VCV931610

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9355 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atelosteogenesis type III

Computational evidence

Protein change
AlphaMissense	0.9355	likely pathogenic
REVEL	0.879	moderately pathogenic-leaning
SaProt	LLR -13.38	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,014 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00103% 15/1,461,844 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,014
European (non-Finnish)	0.0011%	90,767
South Asian	0.0011%	91,072

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.Thr806Lys
Coding: c.2417C>A
MANE Select: NM_001457
dbSNP: rs940585956
Type: single nucleotide variant
Location: chr3:58110103 (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

atelosteogenesis type III — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNB p.Thr806Ala Uncertain significance ★ ⚠ same residue
FLNB p.Thr806= Likely benign ★ same residue
FLNB p.Thr806Met Likely benign ★ same residue
FLNB p.Gly168Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
FLNB p.Gly1691Ser Pathogenic ★★ ⚠ same condition
FLNB c.3724+4G>C Uncertain significance ★★ same condition
FLNB p.Ala259Val Uncertain significance ★★ ⚠ same condition
FLNB p.Arg2289His 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-thr806lys (accessed [today's date]).

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