Is FLNB p.Phe2214= (c.6642C>T) pathogenic?

FLNB p.Phe2214= (c.6642C>T) is classified Benign/Likely benign in FLNB (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-03-01). Low-frequency (popmax 2.6%, mid); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Phe2214= (c.6642C>T)?

FLNB p.Phe2214= (c.6642C>T) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Phe2214= (c.6642C>T) in the general population?

FLNB p.Phe2214= (c.6642C>T) is low-frequency (popmax 2.6%, mid) (gnomAD).

FLNB p.Phe2214=

c.6642C>T · rs140786324 · VCV288202

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.6%, mid)

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 1.4	GERP -0.16, phastCons 1
Overall
CADD	11.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.6% Middle Eastern · 157/6,036 alleles

Filtering AF 2.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.14%

Overall 0.111% 1,793/1,613,982 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.6%	38
Ashkenazi Jewishnot grpmax-eligible	1.06%	94
Admixed American	0.372%	269
Remaining individualsnot grpmax-eligible	0.277%	361
South Asian	0.0758%	1,320
European (non-Finnish)	0.0699%	1,430
African / African-American	0.0387%	2,586
East Asian	0.00223%	44,864
Finnishnot grpmax-eligible	0.00156%	64,010

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.Phe2214=
Coding: c.6642C>T
MANE Select: NM_001457
dbSNP: rs140786324
Type: single nucleotide variant
Location: chr3:58154798 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 2214: a β-strand; the 'interaction with flna 1' region; 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

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-phe2214 (accessed [today's date]).

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