Is FLNB p.Ala2482Pro (c.7444G>C) pathogenic?

FLNB p.Ala2482Pro (c.7444G>C) is classified Uncertain significance in FLNB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). AlphaMissense: likely benign (0.1035); Very rare (popmax 0.00833%, amr).

How common is FLNB p.Ala2482Pro (c.7444G>C) in the general population?

FLNB p.Ala2482Pro (c.7444G>C) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about FLNB p.Ala2482Pro (c.7444G>C)?

AlphaMissense predicts likely benign (score 0.1035) — an in-silico prediction, not a clinical call.

FLNB p.Ala2482Pro

c.7444G>C · rs201566479 · VCV1986357

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1035 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1035	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -6.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -5.7, phastCons 0.64
Regional constraint	o/e 0.82	unconstrained · MANE · 32 kb · p 1.7e-10 · regional, not allelic
Overall
CADD	15.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00833% Admixed American · 5/60,032 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.000558% 9/1,614,148 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,006
Remaining individualsnot grpmax-eligible	0.0016%	62,506
South Asian	0.0011%	91,084
European (non-Finnish)	0.000169%	589,998

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.Ala2482Pro
Coding: c.7444G>C
MANE Select: NM_001457
dbSNP: rs201566479
Type: single nucleotide variant
Location: chr3:58169616 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2482: an α-helix; the 'interaction with inppl1' region; the 'self-association site, tail' region; the 'hinge 2' region

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

Similar variants

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FLNB p.Arg1948Ter Pathogenic ★★ same type
FLNB p.Arg649Ter Pathogenic ★★ same type
FLNB p.Asp167Gly Likely pathogenic ★★ same type
FLNB p.Glu227Lys Pathogenic ★★ same type
FLNB p.Gly168Ser Pathogenic/Likely 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-ala2482pro (accessed [today's date]).

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