Is FLNB p.Phe1390= (c.4170C>T) pathogenic?

FLNB p.Phe1390= (c.4170C>T) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-07-14). Ultra-rare (popmax 0.0582%, sas); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Phe1390= (c.4170C>T)?

FLNB p.Phe1390= (c.4170C>T) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Phe1390= (c.4170C>T) in the general population?

FLNB p.Phe1390= (c.4170C>T) is ultra-rare (popmax 0.0582%, sas) (gnomAD).

FLNB p.Phe1390=

c.4170C>T · rs374070003 · VCV902328

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0582%, sas)

Conditions

FLNB-Related Spectrum Disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.79	GERP -5.4, phastCons 0.017
Overall
CADD	6.463	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0582% South Asian · 53/91,072 alleles

Filtering AF 0.0457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.00601% 97/1,613,964 alleles · ultra-rare exomes 89/1,461,722 · genomes 8/152,242 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0582%	1,718
East Asian	0.0245%	4,080
Remaining individualsnot grpmax-eligible	0.0176%	5,682
European (non-Finnish)	0.0017%	58,994
Finnishnot grpmax-eligible	0.00156%	64,028
African / African-American	0.00133%	75,020

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.Phe1390=
Coding: c.4170C>T
MANE Select: NM_001457
dbSNP: rs374070003
Type: single nucleotide variant
Location: chr3:58126710 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1390: the 'interaction with fblp1' region

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

Disease context

FLNB-Related Spectrum Disorders

Similar variants

FLNB p.Glu1661Lys Uncertain significance ★★ ⚠ same condition
FLNB p.Glu78Gly Uncertain significance ★★ ⚠ same condition
FLNB p.His1117Arg Uncertain significance ★★ ⚠ same condition
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-phe1390 (accessed [today's date]).

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