Is FLNA p.Ile2364= (c.7092C>A) pathogenic?

FLNA p.Ile2364= (c.7092C>A) is classified Conflicting classifications of pathogenicity in FLNA (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0738%, sas); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with FLNA p.Ile2364= (c.7092C>A)?

FLNA p.Ile2364= (c.7092C>A) is associated with familial thoracic aortic aneurysm and aortic dissection, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Ile2364= (c.7092C>A) in the general population?

FLNA p.Ile2364= (c.7092C>A) is ultra-rare (popmax 0.0738%, sas) (gnomAD).

FLNA p.Ile2364=

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.7092C>A · rs782591917 · VCV498632

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0738%, sas)

Conditions

familial thoracic aortic aneurysm and aortic dissection

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 -0.55	GERP -3.7
Overall
CADD	5.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0738% South Asian · 42/56,886 alleles

Filtering AF 0.0561% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0499%

Overall 0.00604% 73/1,209,545 alleles · ultra-rare exomes 72/1,097,077 · genomes 1/112,468 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0738%	1,354
Middle Eastern	0.0458%	2,185
Remaining individualsnot grpmax-eligible	0.0105%	9,514
European (non-Finnish)	0.00268%	37,264

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: FLNA
Protein: p.Ile2364=
Coding: c.7092C>A
MANE Select: NM_001110556
dbSNP: rs782591917
Type: single nucleotide variant
Location: chrX:154350973 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB

Full FLNA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: heterotopia, periventricular, X-linked dominant otopalatodigital syndrome type 2 Melnick-Needles syndrome frontometaphyseal dysplasia

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

FLNA c.1066-1G>A Pathogenic/Likely pathogenic ★★ same condition
FLNA c.2022+1G>A Pathogenic ★★ same condition
FLNA c.4598+1G>A Pathogenic/Likely pathogenic ★★ same condition
FLNA c.5417-2A>G Likely pathogenic ★★ same condition
FLNA c.868+1G>A Likely pathogenic ★★ same condition
FLNA c.987+1G>A Likely pathogenic ★★ same condition
FLNA p.Ala1188Thr Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Arg1515Ter 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/flna-p-ile2364 (accessed [today's date]).

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