Is FLNB p.His426= (c.1278C>T) pathogenic?

FLNB p.His426= (c.1278C>T) is classified Benign/Likely benign in FLNB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-28). Rare (popmax 0.503%, sas); Associated with connective tissue disorder.

What condition is associated with FLNB p.His426= (c.1278C>T)?

FLNB p.His426= (c.1278C>T) is associated with connective tissue disorder (ClinVar).

How common is FLNB p.His426= (c.1278C>T) in the general population?

FLNB p.His426= (c.1278C>T) is rare (popmax 0.503%, sas) (gnomAD).

FLNB p.His426=

c.1278C>T · rs572259451 · VCV346308

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.503%, sas)

Conditions

connective tissue disorder

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 -11	GERP -5.4
Overall
CADD	3.124	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.503% South Asian · 458/91,084 alleles

Filtering AF 0.465% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.45%

Overall 0.0367% 593/1,614,158 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.503%	199
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.0528%	1,894
Admixed American	0.0433%	2,308
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
African / African-American	0.012%	8,336
European (non-Finnish)	0.00449%	22,265
East Asian	0.00223%	44,884

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.His426=
Coding: c.1278C>T
MANE Select: NM_001457
dbSNP: rs572259451
Type: single nucleotide variant
Location: chr3:58098841 (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.His426Gln Uncertain significance ★ ⚠ same residue
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

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-his426 (accessed [today's date]).

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