Is FLNB p.Pro1407= (c.4221C>T) pathogenic?

FLNB p.Pro1407= (c.4221C>T) is classified Benign in FLNB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 98.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Pro1407= (c.4221C>T)?

FLNB p.Pro1407= (c.4221C>T) is associated with FLNB-Related Spectrum Disorders (ClinVar).

FLNB p.Pro1407=

Q: How common is FLNB p.Pro1407= (c.4221C>T) in the general population?

FLNB p.Pro1407= (c.4221C>T) is common (popmax 98.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4221C>T · rs2362904 · VCV258111

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 98.1%, eas) — too common for a highly-penetrant pathogenic allele

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 -3.8	GERP -5
Overall
CADD	10.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 98.1% East Asian · 44,023/44,864 alleles

Filtering AF 97.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 97%

Overall 31.9% 513,477/1,610,188 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	98.1%	1
African / African-American	71.7%	1
Admixed American	52.3%	2
South Asian	48.8%	2
Remaining individualsnot grpmax-eligible	35.7%	3
Amishnot grpmax-eligible	30.9%	3
Middle Eastern	29.3%	3
Finnishnot grpmax-eligible	26%	4
European (non-Finnish)	24.8%	4
Ashkenazi Jewishnot grpmax-eligible	24.3%	4

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.Pro1407=
Coding: c.4221C>T
MANE Select: NM_001457
dbSNP: rs2362904
Type: single nucleotide variant
Location: chr3:58126761 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1407: 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-pro1407 (accessed [today's date]).

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