Is FLNA p.Ser2510= (c.7530C>T) pathogenic?

FLNA p.Ser2510= (c.7530C>T) is classified Likely benign in FLNA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-05). Ultra-rare (popmax 0.0443%, eas); Associated with heterotopia, periventricular, X-linked dominant.

What condition is associated with FLNA p.Ser2510= (c.7530C>T)?

FLNA p.Ser2510= (c.7530C>T) is associated with heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Ser2510= (c.7530C>T) in the general population?

FLNA p.Ser2510= (c.7530C>T) is ultra-rare (popmax 0.0443%, eas) (gnomAD).

FLNA p.Ser2510=

c.7530C>T · rs782602947 · VCV589866

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0443%, eas)

Conditions

heterotopia, periventricular, X-linked dominant

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 1.6	GERP -0.39, phastCons 1
Overall
CADD	9.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0443% East Asian · 15/33,877 alleles

Filtering AF 0.0272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.022%

Overall 0.00149% 18/1,211,983 alleles · ultra-rare exomes 18/1,097,614 · genomes 0/114,369 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0443%	2,258
Admixed American	0.00433%	23,081
European (non-Finnish)	0.000112%	895,448

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.Ser2510=
Coding: c.7530C>T
MANE Select: NM_001110556
dbSNP: rs782602947
Type: single nucleotide variant
Location: chrX:154349671 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 2510: a modified residue (phosphoserine)

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

Disease context

heterotopia, periventricular, X-linked dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: otopalatodigital syndrome type 2 Melnick-Needles syndrome frontometaphyseal dysplasia familial thoracic aortic aneurysm and aortic dissection

Similar variants

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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-ser2510 (accessed [today's date]).

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