Is FLNA p.Pro2036= (c.6108G>A) pathogenic?

FLNA p.Pro2036= (c.6108G>A) is classified Conflicting classifications of pathogenicity in FLNA (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-05-15). Very rare (popmax 0.00872%, afr); Associated with Melnick-Needles syndrome.

What condition is associated with FLNA p.Pro2036= (c.6108G>A)?

FLNA p.Pro2036= (c.6108G>A) is associated with Melnick-Needles syndrome, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Pro2036= (c.6108G>A) in the general population?

FLNA p.Pro2036= (c.6108G>A) is very rare (popmax 0.00872%, afr) (gnomAD).

FLNA p.Pro2036=

c.6108G>A · rs782221205 · VCV281630

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00872%, afr)

Conditions

Melnick-Needles syndrome

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 -20	GERP -3.7
Overall
CADD	0.013	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00872% African / African-American · 5/57,315 alleles

Filtering AF 0.00338% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00215%

Overall 0.0019% 23/1,209,950 alleles · very rare exomes 20/1,097,558 · genomes 3/112,392 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00872%	11,463
Finnishnot grpmax-eligible	0.00216%	46,268
European (non-Finnish)	0.00179%	55,944
South Asian	0.00176%	56,906

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.Pro2036=
Coding: c.6108G>A
MANE Select: NM_001110556
dbSNP: rs782221205
Type: single nucleotide variant
Location: chrX:154353119 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 2036: a β-strand

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

Similar variants

FLNA p.Pro2036Leu Uncertain significance ★★ ⚠ same residue
FLNA p.Pro2036Ser Uncertain significance ★ ⚠ same residue
FLNA p.Pro2036Thr Uncertain significance ★ ⚠ same residue
FLNA p.Pro2036Arg Likely benign ★ 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

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-pro2036 (accessed [today's date]).

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