Is FLNA p.Ser194= (c.582C>T) pathogenic?

FLNA p.Ser194= (c.582C>T) is classified Likely benign in FLNA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-15). Very rare (popmax 0.00175%, sas); Associated with otopalatodigital syndrome type 2.

What condition is associated with FLNA p.Ser194= (c.582C>T)?

FLNA p.Ser194= (c.582C>T) is associated with otopalatodigital syndrome type 2, heterotopia, periventricular, X-linked dominant, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Ser194= (c.582C>T) in the general population?

FLNA p.Ser194= (c.582C>T) is very rare (popmax 0.00175%, sas) (gnomAD).

FLNA p.Ser194=

c.582C>T · rs1400462134 · VCV2051820

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00175%, sas)

Conditions

otopalatodigital syndrome type 2

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 -9.9	GERP -3.7
Overall
CADD	0.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% South Asian · 1/57,022 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000456% 5/1,097,238 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00175%	57,022
African / African-American	0.00173%	57,866
European (non-Finnish)	0.000335%	298,418

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.Ser194=
Coding: c.582C>T
MANE Select: NM_001110556
dbSNP: rs1400462134
Type: single nucleotide variant
Location: chrX:154367882 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 194: a β-strand; the 'actin-binding' region; the calponin-homology (ch) 2 domain

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 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
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-ser194 (accessed [today's date]).

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