Is FLNB p.Phe2347Leu (c.7041C>A) pathogenic?

FLNB p.Phe2347Leu (c.7041C>A) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-19). AlphaMissense: likely pathogenic (0.9961); Ultra-rare (popmax 0.0604%, sas); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Phe2347Leu (c.7041C>A)?

FLNB p.Phe2347Leu (c.7041C>A) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Phe2347Leu (c.7041C>A) in the general population?

FLNB p.Phe2347Leu (c.7041C>A) is ultra-rare (popmax 0.0604%, sas) (gnomAD).

What do computational predictors say about FLNB p.Phe2347Leu (c.7041C>A)?

AlphaMissense predicts likely pathogenic (score 0.9961) — an in-silico prediction, not a clinical call.

FLNB p.Phe2347Leu

c.7041C>A · rs139325959 · VCV346361

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9961 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0604%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FLNB-Related Spectrum Disorders

Computational evidence

Protein change
AlphaMissense	0.9961	likely pathogenic · top 2% in FLNB
REVEL	0.819	moderately pathogenic-leaning
SaProt	LLR -10.99	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 2.2	GERP -2.5, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 32 kb · p 1.7e-10 · regional, not allelic
Overall
CADD	23.9	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 0.0604% South Asian · 55/91,088 alleles

Filtering AF 0.0509% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0495%

Overall 0.0476% 768/1,614,216 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0604%	1,656
European (non-Finnish)	0.0544%	1,838
Middle Eastern	0.0495%	2,021
Admixed American	0.045%	2,224
Remaining individualsnot grpmax-eligible	0.0432%	2,315
Finnishnot grpmax-eligible	0.0172%	5,822
African / African-American	0.004%	25,019

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.Phe2347Leu
Coding: c.7041C>A
MANE Select: NM_001457
dbSNP: rs139325959
Type: single nucleotide variant
Location: chr3:58163173 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2347: 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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FLNB p.Leu1440Pro Uncertain significance ★★ ⚠ same condition
FLNB p.Pro396Ser Uncertain significance ★★ ⚠ same condition
FLNB p.Ser1096Phe Uncertain significance ★★ ⚠ same condition
FLNB p.Ser188Cys Uncertain significance ★★ ⚠ same condition
FLNB p.Tyr63His 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-phe2347leu (accessed [today's date]).

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