Is FLNA p.Ser1279= (c.3837T>C) pathogenic?

FLNA p.Ser1279= (c.3837T>C) is classified Likely benign in FLNA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-28). Very rare (popmax 0.00175%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with FLNA p.Ser1279= (c.3837T>C)?

FLNA p.Ser1279= (c.3837T>C) 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.Ser1279= (c.3837T>C) in the general population?

FLNA p.Ser1279= (c.3837T>C) is very rare (popmax 0.00175%, afr) (gnomAD).

FLNA p.Ser1279=

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.3837T>C · rs782180714 · VCV1455293

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

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 -6.8	GERP -3.1
Overall
CADD	2.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% African / African-American · 1/57,255 alleles

Filtering AF 0.000241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000158%

Overall 0.000579% 7/1,209,315 alleles · very rare exomes 6/1,097,127 · genomes 1/112,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00175%	57,255
European (non-Finnish)	0.00067%	149,172

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.Ser1279=
Coding: c.3837T>C
MANE Select: NM_001110556
dbSNP: rs782180714
Type: single nucleotide variant
Location: chrX:154359874 (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 p.Ser1279Asn Uncertain significance ★ ⚠ same residue
FLNA p.Ser1279Gly Uncertain significance ★ ⚠ same residue
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

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-ser1279 (accessed [today's date]).

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