Is FLNA p.Tyr287Cys (c.860A>G) pathogenic?

FLNA p.Tyr287Cys (c.860A>G) is classified Uncertain significance in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-17). AlphaMissense: likely pathogenic (0.6177); Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with FLNA p.Tyr287Cys (c.860A>G)?

FLNA p.Tyr287Cys (c.860A>G) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is FLNA p.Tyr287Cys (c.860A>G) in the general population?

FLNA p.Tyr287Cys (c.860A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNA p.Tyr287Cys (c.860A>G)?

AlphaMissense predicts likely pathogenic (score 0.6177) — an in-silico prediction, not a clinical call.

FLNA p.Tyr287Cys

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.860A>G · VCV4871441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6177 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial thoracic aortic aneurysm and aortic dissection

Computational evidence

Protein change
AlphaMissense	0.6177	likely pathogenic
REVEL	0.831	moderately pathogenic-leaning
SaProt	LLR -12.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 4,344 bp · p 1.3e-27 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLNA
Protein: p.Tyr287Cys
Coding: c.860A>G
MANE Select: NM_001110556
Type: single nucleotide variant
Location: chrX:154367405 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 287: the 'disordered' 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.Tyr287= Benign/Likely benign ★★ same residue
FLNA p.Tyr287Ter Likely pathogenic ★ 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-tyr287cys (accessed [today's date]).

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