Is FLNA p.Pro817= (c.2451C>T) pathogenic?

FLNA p.Pro817= (c.2451C>T) is classified Benign/Likely benign in FLNA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-20). Ultra-rare (popmax 0.023%, mid); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with FLNA p.Pro817= (c.2451C>T)?

FLNA p.Pro817= (c.2451C>T) 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.Pro817= (c.2451C>T) in the general population?

FLNA p.Pro817= (c.2451C>T) is ultra-rare (popmax 0.023%, mid) (gnomAD).

FLNA p.Pro817=

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.2451C>T · rs782192587 · VCV757689

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

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 -15	GERP -3.4
Overall
CADD	0.184	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.023% Middle Eastern · 1/4,354 alleles

Filtering AF 0.00081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000624%

Overall 0.00149% 18/1,211,291 alleles · ultra-rare exomes 18/1,097,296 · genomes 0/113,995 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.023%	4,354
Admixed American	0.00217%	46,100
Remaining individualsnot grpmax-eligible	0.0021%	47,636
South Asian	0.00175%	57,044
African / African-American	0.00173%	57,914
European (non-Finnish)	0.00145%	68,875

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.Pro817=
Coding: c.2451C>T
MANE Select: NM_001110556
dbSNP: rs782192587
Type: single nucleotide variant
Location: chrX:154362532 (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.Pro817Ser Conflicting classifications of pathogenicity ★ ⚠ 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
FLNA p.Ala1188Thr Pathogenic/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-pro817 (accessed [today's date]).

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