Is FLNA p.Asp156= (c.468C>T) pathogenic?

FLNA p.Asp156= (c.468C>T) is classified Likely benign in FLNA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-23). Very rare (popmax 0.00176%, sas); Associated with heterotopia, periventricular, X-linked dominant.

What condition is associated with FLNA p.Asp156= (c.468C>T)?

FLNA p.Asp156= (c.468C>T) is associated with heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Asp156= (c.468C>T) in the general population?

FLNA p.Asp156= (c.468C>T) is very rare (popmax 0.00176%, sas) (gnomAD).

FLNA p.Asp156=

c.468C>T · rs782657089 · VCV1742454

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00176%, sas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	3.365	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00176% South Asian · 1/56,737 alleles

Filtering AF 0.000242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00058% 7/1,206,965 alleles · very rare exomes 6/1,095,538 · genomes 1/111,427 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00176%	56,737
European (non-Finnish)	0.000672%	148,800

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.Asp156=
Coding: c.468C>T
MANE Select: NM_001110556
dbSNP: rs782657089
Type: single nucleotide variant
Location: chrX:154367996 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 156: the 'actin-binding' region

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.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-asp156 (accessed [today's date]).

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