Is FLNB p.Pro1026= (c.3078C>T) pathogenic?

FLNB p.Pro1026= (c.3078C>T) is classified Benign in FLNB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-18). Low-frequency (popmax 1.35%, afr); Associated with connective tissue disorder.

What condition is associated with FLNB p.Pro1026= (c.3078C>T)?

FLNB p.Pro1026= (c.3078C>T) is associated with connective tissue disorder (ClinVar).

How common is FLNB p.Pro1026= (c.3078C>T) in the general population?

FLNB p.Pro1026= (c.3078C>T) is low-frequency (popmax 1.35%, afr) (gnomAD).

FLNB p.Pro1026=

c.3078C>T · rs147267045 · VCV258104

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.35%, afr)

Conditions

connective tissue disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -5.4
Overall
CADD	0.385	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.35% African / African-American · 1,016/75,024 alleles

Filtering AF 1.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.26%

Overall 0.0908% 1,466/1,614,110 alleles · low-frequency exomes 836/1,461,838 · genomes 630/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.35%	74
Admixed American	0.143%	698
Remaining individualsnot grpmax-eligible	0.123%	812
European (non-Finnish)	0.0236%	4,229
Middle Eastern	0.0165%	6,062
East Asian	0.0111%	8,976
South Asian	0.0022%	45,543

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.Pro1026=
Coding: c.3078C>T
MANE Select: NM_001457
dbSNP: rs147267045
Type: single nucleotide variant
Location: chr3:58121455 (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

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNB p.Phe161Cys Likely pathogenic ★★ same condition
FLNB p.Gly496Cys Uncertain significance ★★ ⚠ same condition
FLNB p.Thr1003Met Uncertain significance ★★ ⚠ same condition
FLNB p.Thr1579Ile Uncertain significance ★★ ⚠ same condition
FLNB c.1611-4G>A Benign ★★ same condition
FLNB c.292+8C>A Benign/Likely benign ★★ same condition
FLNB c.4222+8A>G Benign/Likely benign ★★ same condition
FLNB c.5426-10G>A Benign/Likely benign ★★ 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-pro1026 (accessed [today's date]).

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