Is FLNA p.Pro2647= (c.7941C>T) pathogenic?

FLNA p.Pro2647= (c.7941C>T) is classified Likely benign in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-30). Very rare (popmax 0.00173%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with FLNA p.Pro2647= (c.7941C>T)?

FLNA p.Pro2647= (c.7941C>T) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is FLNA p.Pro2647= (c.7941C>T) in the general population?

FLNA p.Pro2647= (c.7941C>T) is very rare (popmax 0.00173%, afr) (gnomAD).

FLNA p.Pro2647=

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.7941C>T · rs2522710851 · VCV1761201

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00173%, 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 2.5	GERP -1.6, phastCons 1
Overall
CADD	11.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00173% African / African-American · 1/57,752 alleles

Overall 8.31e-05% 1/1,203,475 alleles · very rare exomes 1/1,089,700 · genomes 0/113,775 · joint denominator

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.Pro2647=
Coding: c.7941C>T
MANE Select: NM_001110556
dbSNP: rs2522710851
Type: single nucleotide variant
Location: chrX:154348852 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 2647: the 'self-association site, tail' 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-pro2647 (accessed [today's date]).

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