Is FLNA p.Pro1591= (c.4773G>A) pathogenic?

FLNA p.Pro1591= (c.4773G>A) is classified Likely benign in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-26). Very rare (popmax 0.00217%, amr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with FLNA p.Pro1591= (c.4773G>A)?

FLNA p.Pro1591= (c.4773G>A) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is FLNA p.Pro1591= (c.4773G>A) in the general population?

FLNA p.Pro1591= (c.4773G>A) is very rare (popmax 0.00217%, amr) (gnomAD).

FLNA p.Pro1591=

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.4773G>A · rs942277128 · VCV1742985

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

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 0.8	GERP -1.9, phastCons 1
Overall
CADD	7.257	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00217% Admixed American · 1/46,120 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.00033% 4/1,211,657 alleles · very rare exomes 4/1,097,524 · genomes 0/114,133 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00217%	46,120
Remaining individualsnot grpmax-eligible	0.0021%	47,631
European (non-Finnish)	0.000223%	447,668

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.Pro1591=
Coding: c.4773G>A
MANE Select: NM_001110556
dbSNP: rs942277128
Type: single nucleotide variant
Location: chrX:154357606 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 1591: the 'interaction with furin' region

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

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

FLNA p.Pro1591Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNA p.Pro1591Arg Uncertain significance ★ same residue
FLNA p.Gln2546Ter Pathogenic ★★ same condition
FLNA p.Gly1554Arg Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Pro207Leu Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Thr1739= Pathogenic ★★ same condition
FLNA c.2826+4G>A Uncertain significance ★★ same condition
FLNA c.3979+4C>T 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/flna-p-pro1591 (accessed [today's date]).

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