Is FLNA p.Ala13= (c.39A>G) pathogenic?

FLNA p.Ala13= (c.39A>G) is classified Likely benign in FLNA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-02-02). Very rare (popmax 0.00362%, sas); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with FLNA p.Ala13= (c.39A>G)?

FLNA p.Ala13= (c.39A>G) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is FLNA p.Ala13= (c.39A>G) in the general population?

FLNA p.Ala13= (c.39A>G) is very rare (popmax 0.00362%, sas) (gnomAD).

FLNA p.Ala13=

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.39A>G · rs782146314 · VCV389246

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00362%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.24	GERP -2.4, phastCons 0.042
Overall
CADD	12.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00362% South Asian · 2/55,198 alleles

Filtering AF 0.000601% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000225%

Overall 0.000417% 5/1,197,770 alleles · very rare exomes 5/1,083,713 · genomes 0/114,057 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00362%	27,599
European (non-Finnish)	0.000337%	296,417

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.Ala13=
Coding: c.39A>G
MANE Select: NM_001110556
dbSNP: rs782146314
Type: single nucleotide variant
Location: chrX:154371207 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 13: the 'disordered' region; the 'actin-binding' 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.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
FLNA c.720+4C>T Uncertain significance ★★ same condition
FLNA p.Ala1061Thr 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-ala13 (accessed [today's date]).

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