Is FLNB p.Asp348= (c.1044C>T) pathogenic?

FLNB p.Asp348= (c.1044C>T) is classified Benign/Likely benign in FLNB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-21). Rare (popmax 0.838%, afr); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Asp348= (c.1044C>T)?

FLNB p.Asp348= (c.1044C>T) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Asp348= (c.1044C>T) in the general population?

FLNB p.Asp348= (c.1044C>T) is rare (popmax 0.838%, afr) (gnomAD).

FLNB p.Asp348=

c.1044C>T · rs111996979 · VCV497262

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.838%, afr)

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 2.2	GERP 1.8, phastCons 1
Overall
CADD	13.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.838% African / African-American · 629/75,034 alleles

Filtering AF 0.784% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.762%

Overall 0.0512% 826/1,614,122 alleles · rare exomes 469/1,461,838 · genomes 357/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.838%	119
Middle Eastern	0.297%	336
Remaining individualsnot grpmax-eligible	0.0928%	1,078
Admixed American	0.0467%	2,143
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,961
European (non-Finnish)	0.00661%	15,128
South Asian	0.00549%	18,212

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.Asp348=
Coding: c.1044C>T
MANE Select: NM_001457
dbSNP: rs111996979
Type: single nucleotide variant
Location: chr3:58097874 (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

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-asp348 (accessed [today's date]).

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