Is FLNB p.Ile2310Val (c.6928A>G) pathogenic?

FLNB p.Ile2310Val (c.6928A>G) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-19). AlphaMissense: likely benign (0.0983); Rare (popmax 0.128%, afr); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Ile2310Val (c.6928A>G)?

FLNB p.Ile2310Val (c.6928A>G) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Ile2310Val (c.6928A>G) in the general population?

FLNB p.Ile2310Val (c.6928A>G) is rare (popmax 0.128%, afr) (gnomAD).

What do computational predictors say about FLNB p.Ile2310Val (c.6928A>G)?

AlphaMissense predicts likely benign (score 0.0983) — an in-silico prediction, not a clinical call.

FLNB p.Ile2310Val

c.6928A>G · rs143005300 · VCV902476

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0983 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.128%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

FLNB-Related Spectrum Disorders

Computational evidence

Protein change
AlphaMissense	0.0983	likely benign
REVEL	0.393	indeterminate
SaProt	LLR -5.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.77 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 2.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 32 kb · p 1.7e-10 · regional, not allelic
Overall
CADD	24.4	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 0.128% African / African-American · 96/75,054 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0995%

Overall 0.00682% 110/1,614,072 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.128%	782
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Admixed American	0.005%	20,010
East Asian	0.00223%	44,880
European (non-Finnish)	0.000254%	393,311

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.Ile2310Val
Coding: c.6928A>G
MANE Select: NM_001457
dbSNP: rs143005300
Type: single nucleotide variant
Location: chr3:58159593 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2310: a β-strand; the 'interaction with inppl1' region

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

Disease context

FLNB-Related Spectrum Disorders

Similar variants

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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-ile2310val (accessed [today's date]).

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