Is FLNA p.Glu392= (c.1176G>A) pathogenic?

FLNA p.Glu392= (c.1176G>A) is classified Benign/Likely benign in FLNA (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-03). Rare (popmax 0.846%, nfe); Associated with frontometaphyseal dysplasia.

What condition is associated with FLNA p.Glu392= (c.1176G>A)?

FLNA p.Glu392= (c.1176G>A) is associated with frontometaphyseal dysplasia, connective tissue disorder, intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked (ClinVar).

How common is FLNA p.Glu392= (c.1176G>A) in the general population?

FLNA p.Glu392= (c.1176G>A) is rare (popmax 0.846%, nfe) (gnomAD).

How is Frontometaphyseal dysplasia inherited?

Typically Autosomal dominant, X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

FLNA p.Glu392=

c.1176G>A · rs201173693 · VCV129065

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

rare (popmax 0.846%, nfe)

Conditions

frontometaphyseal dysplasia

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 -2.8	GERP -3
Overall
CADD	7.647	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.846% European (non-Finnish) · 7,572/895,421 alleles

Filtering AF 0.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.823%

Overall 0.688% 8,336/1,211,157 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.912%	110
European (non-Finnish)grpmax	0.846%	118
Remaining individualsnot grpmax-eligible	0.477%	210
Admixed American	0.224%	447
Finnishnot grpmax-eligible	0.22%	454
South Asian	0.151%	662
African / African-American	0.073%	1,370
Middle Eastern	0.0459%	2,178

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu392=
Coding: c.1176G>A
MANE Select: NM_001110556
dbSNP: rs201173693
Type: single nucleotide variant
Location: chrX:154366360 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB

Full FLNA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

frontometaphyseal dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: connective tissue disorder intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked heterotopia, periventricular, X-linked dominant terminal osseous dysplasia-pigmentary defects syndrome FG syndrome 2 otopalatodigital syndrome type 2 Melnick-Needles syndrome otopalatodigital syndrome type 1 cardiac valvular dysplasia, X-linked familial thoracic aortic aneurysm and aortic dissection frontometaphyseal dysplasia 1

For Frontometaphyseal dysplasia (Orphanet):

Inheritance: Autosomal dominant, X-linked dominant
Onset: Neonatal

Similar variants

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
FLNA p.Arg1515Ter 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-glu392 (accessed [today's date]).

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