Is FLNA p.Pro1773= (c.5319G>A) pathogenic?

FLNA p.Pro1773= (c.5319G>A) is classified Benign/Likely benign in FLNA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-13). Ultra-rare (popmax 0.0316%, sas); Associated with Melnick-Needles syndrome.

What condition is associated with FLNA p.Pro1773= (c.5319G>A)?

FLNA p.Pro1773= (c.5319G>A) is associated with Melnick-Needles syndrome, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Pro1773= (c.5319G>A) in the general population?

FLNA p.Pro1773= (c.5319G>A) is ultra-rare (popmax 0.0316%, sas) (gnomAD).

FLNA p.Pro1773=

c.5319G>A · rs782127738 · VCV695614

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0316%, sas)

Conditions

Melnick-Needles syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.261	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.4	GERP -3.4
Overall
CADD	1.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0316% South Asian · 18/56,891 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0168%

Overall 0.00314% 38/1,209,027 alleles · ultra-rare exomes 35/1,095,662 · genomes 3/113,365 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0316%	3,161
Admixed American	0.00652%	15,346
East Asian	0.00296%	33,796
European (non-Finnish)	0.00179%	55,870

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.Pro1773=
Coding: c.5319G>A
MANE Select: NM_001110556
dbSNP: rs782127738
Type: single nucleotide variant
Location: chrX:154354478 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 1773: the 'hinge 1' region

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

Disease context

Melnick-Needles syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: heterotopia, periventricular, X-linked dominant otopalatodigital syndrome type 2 frontometaphyseal dysplasia familial thoracic aortic aneurysm and aortic dissection

Similar variants

FLNA p.Pro1773Leu 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-pro1773 (accessed [today's date]).

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