Is FLNB p.Asn369= (c.1107C>T) pathogenic?

FLNB p.Asn369= (c.1107C>T) is classified Benign/Likely benign in FLNB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-03). Rare (popmax 0.619%, sas); Associated with connective tissue disorder.

What condition is associated with FLNB p.Asn369= (c.1107C>T)?

FLNB p.Asn369= (c.1107C>T) is associated with connective tissue disorder (ClinVar).

How common is FLNB p.Asn369= (c.1107C>T) in the general population?

FLNB p.Asn369= (c.1107C>T) is rare (popmax 0.619%, sas) (gnomAD).

FLNB p.Asn369=

c.1107C>T · rs538953239 · VCV720245

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.619%, 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 -0.26	GERP -1.3, phastCons 0.19
Overall
CADD	9.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.619% South Asian · 564/91,080 alleles

Filtering AF 0.577% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.56%

Overall 0.0369% 596/1,614,134 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.619%	161
Remaining individualsnot grpmax-eligible	0.0432%	2,315
African / African-American	0.00267%	37,519
Admixed American	0.00167%	60,020
European (non-Finnish)	0.000169%	590,002

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.Asn369=
Coding: c.1107C>T
MANE Select: NM_001457
dbSNP: rs538953239
Type: single nucleotide variant
Location: chr3:58097937 (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.Asn369Asp 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-asn369 (accessed [today's date]).

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