Is FLNB p.Ile264= (c.792C>T) pathogenic?

FLNB p.Ile264= (c.792C>T) is classified Benign in FLNB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Common (popmax 8.74%, afr) — too common for a highly-penetrant pathogenic allele; Associated with connective tissue disorder.

What condition is associated with FLNB p.Ile264= (c.792C>T)?

FLNB p.Ile264= (c.792C>T) is associated with connective tissue disorder (ClinVar).

FLNB p.Ile264=

Q: How common is FLNB p.Ile264= (c.792C>T) in the general population?

FLNB p.Ile264= (c.792C>T) is common (popmax 8.74%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.792C>T · rs7623314 · VCV346302

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 8.74%, afr) — too common for a highly-penetrant pathogenic allele

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	all four deltas below 0.2 · C>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.3	GERP -5.4
Overall
CADD	10.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.74% African / African-American · 6,551/74,944 alleles

Filtering AF 8.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.49%

Overall 0.488% 7,870/1,613,618 alleles · common exomes 4,014/1,461,458 · genomes 3,856/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.74%	11
Remaining individualsnot grpmax-eligible	0.653%	153
Admixed American	0.573%	174
Middle Eastern	0.511%	196
Ashkenazi Jewishnot grpmax-eligible	0.497%	201
European (non-Finnish)	0.03%	3,332
South Asian	0.0253%	3,959
Finnishnot grpmax-eligible	0.0141%	7,113
East Asian	0.00669%	14,955

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.Ile264=
Coding: c.792C>T
MANE Select: NM_001457
dbSNP: rs7623314
Type: single nucleotide variant
Location: chr3:58094840 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 264: an α-helix; the 'disordered' region

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-ile264 (accessed [today's date]).

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