Is FLNB p.Gln915Glu (c.2743C>G) pathogenic?

FLNB p.Gln915Glu (c.2743C>G) is classified Uncertain significance in FLNB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-09). AlphaMissense: likely benign (0.1235); Absent from gnomAD v4.1; Associated with FLNB-related disorder.

What condition is associated with FLNB p.Gln915Glu (c.2743C>G)?

FLNB p.Gln915Glu (c.2743C>G) is associated with FLNB-related disorder (ClinVar).

How common is FLNB p.Gln915Glu (c.2743C>G) in the general population?

FLNB p.Gln915Glu (c.2743C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNB p.Gln915Glu (c.2743C>G)?

AlphaMissense predicts likely benign (score 0.1235) — an in-silico prediction, not a clinical call.

FLNB p.Gln915Glu

c.2743C>G · rs1159079729 · VCV1000778

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1235 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

FLNB-related disorder

Computational evidence

Protein change
AlphaMissense	0.1235	likely benign
REVEL	0.492	indeterminate
SaProt	LLR -4.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
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	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLNB
Protein: p.Gln915Glu
Coding: c.2743C>G
MANE Select: NM_001457
dbSNP: rs1159079729
Type: single nucleotide variant
Location: chr3:58112316 (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 disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNB p.Gln915Arg Uncertain significance ★★ ⚠ same residue
FLNB p.Arg649Ter Pathogenic ★★ same condition
FLNB p.Glu227Lys Pathogenic ★★ same condition
FLNB p.Gly168Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
FLNB p.Gly1691Ser Pathogenic ★★ ⚠ same condition
FLNB p.Phe2023Ser Likely pathogenic ★★ same condition
FLNB p.Tyr1395Ter Pathogenic/Likely pathogenic ★★ same condition
FLNB p.Arg1438Cys 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-gln915glu (accessed [today's date]).

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