Is FLNB p.Arg1245Trp (c.3733C>T) pathogenic?

FLNB p.Arg1245Trp (c.3733C>T) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.3252); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with FLNB p.Arg1245Trp (c.3733C>T)?

FLNB p.Arg1245Trp (c.3733C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FLNB p.Arg1245Trp (c.3733C>T) in the general population?

FLNB p.Arg1245Trp (c.3733C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about FLNB p.Arg1245Trp (c.3733C>T)?

AlphaMissense predicts likely benign (score 0.3252) — an in-silico prediction, not a clinical call.

FLNB p.Arg1245Trp

c.3733C>T · rs371186570 · VCV2196537

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3252 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3252	likely benign
REVEL	0.847	moderately pathogenic-leaning
SaProt	LLR -8.01	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,898 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00235% 38/1,614,008 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,724
Admixed American	0.005%	20,003
European (non-Finnish)	0.00254%	39,334
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Arg1245Trp
Coding: c.3733C>T
MANE Select: NM_001457
dbSNP: rs371186570
Type: single nucleotide variant
Location: chr3:58124340 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1245: the 'interaction with fblp1' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNB p.Arg1245Pro Uncertain significance ★ ⚠ same residue
FLNB p.Arg1245Gln Likely benign ★ ⚠ same residue
FLNB c.4862-3C>T Uncertain significance ★★ same condition
FLNB p.Ala1191Thr Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1191Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1391Thr Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1427Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1608Val 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-arg1245trp (accessed [today's date]).

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