Is FLNA p.Asp131= (c.393C>T) pathogenic?

FLNA p.Asp131= (c.393C>T) is classified Likely benign in FLNA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0444%, eas); Associated with otopalatodigital syndrome type 2.

What condition is associated with FLNA p.Asp131= (c.393C>T)?

FLNA p.Asp131= (c.393C>T) is associated with otopalatodigital syndrome type 2, heterotopia, periventricular, X-linked dominant, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Asp131= (c.393C>T) in the general population?

FLNA p.Asp131= (c.393C>T) is ultra-rare (popmax 0.0444%, eas) (gnomAD).

FLNA p.Asp131=

c.393C>T · rs782315270 · VCV519886

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0444%, eas)

Conditions

otopalatodigital syndrome type 2

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 -13	GERP -3.7
Overall
CADD	0.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0444% East Asian · 15/33,764 alleles

Filtering AF 0.0273% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0221%

Overall 0.00257% 31/1,207,862 alleles · ultra-rare exomes 29/1,096,434 · genomes 2/111,428 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0444%	2,251
African / African-American	0.00878%	11,385
Admixed American	0.00655%	15,263
European (non-Finnish)	0.000895%	111,737

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.Asp131=
Coding: c.393C>T
MANE Select: NM_001110556
dbSNP: rs782315270
Type: single nucleotide variant
Location: chrX:154368071 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 131: the calponin-homology (ch) 1 domain; the 'actin-binding' region

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

Disease context

otopalatodigital syndrome type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: heterotopia, periventricular, X-linked dominant Melnick-Needles syndrome frontometaphyseal dysplasia familial thoracic aortic aneurysm and aortic dissection

Similar variants

FLNA p.Asp131Glu Uncertain significance ★ ⚠ 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-asp131 (accessed [today's date]).

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