Is FLNB p.Pro841= (c.2523T>G) pathogenic?

FLNB p.Pro841= (c.2523T>G) is classified Benign/Likely benign in FLNB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-29). Low-frequency (popmax 2.26%, sas); Associated with connective tissue disorder.

What condition is associated with FLNB p.Pro841= (c.2523T>G)?

FLNB p.Pro841= (c.2523T>G) is associated with connective tissue disorder, atelosteogenesis type I, atelosteogenesis type III (ClinVar).

How common is FLNB p.Pro841= (c.2523T>G) in the general population?

FLNB p.Pro841= (c.2523T>G) is low-frequency (popmax 2.26%, sas) (gnomAD).

FLNB p.Pro841=

c.2523T>G · rs376893941 · VCV346323

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.26%, 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 0.9	GERP 1.6, phastCons 1
Overall
CADD	12.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.26% South Asian · 2,055/91,082 alleles

Filtering AF 2.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.14%

Overall 0.133% 2,146/1,614,158 alleles · low-frequency exomes 2,029/1,461,848 · genomes 117/152,310 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.26%	44
Remaining individualsnot grpmax-eligible	0.123%	812
Middle Eastern	0.0495%	2,021
East Asian	0.00668%	14,962
Admixed American	0.00333%	30,011
African / African-American	0.00267%	37,522
European (non-Finnish)	0.000339%	295,000

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.Pro841=
Coding: c.2523T>G
MANE Select: NM_001457
dbSNP: rs376893941
Type: single nucleotide variant
Location: chr3:58111829 (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

Also linked: atelosteogenesis type I atelosteogenesis type III Boomerang dysplasia Larsen syndrome spondylocarpotarsal synostosis syndrome

Similar variants

FLNB p.Pro841Ser Uncertain significance ★ ⚠ same residue
FLNB p.Arg1948Ter Pathogenic ★★ same condition
FLNB p.Arg649Ter Pathogenic ★★ same condition
FLNB p.Glu227Lys Pathogenic ★★ same condition
FLNB p.Gly168Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
FLNB p.Gly1691Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
FLNB p.Gly1691Ser Pathogenic ★★ ⚠ same condition
FLNB p.Gly361Asp Pathogenic ★★ 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-pro841 (accessed [today's date]).

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