Is FLNA p.Pro1131= (c.3393C>T) pathogenic?

FLNA p.Pro1131= (c.3393C>T) is classified Likely benign in FLNA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-22). Ultra-rare (popmax 0.0148%, eas); Associated with otopalatodigital syndrome type 2.

What condition is associated with FLNA p.Pro1131= (c.3393C>T)?

FLNA p.Pro1131= (c.3393C>T) is associated with otopalatodigital syndrome type 2, heterotopia, periventricular, X-linked dominant, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Pro1131= (c.3393C>T) in the general population?

FLNA p.Pro1131= (c.3393C>T) is ultra-rare (popmax 0.0148%, eas) (gnomAD).

FLNA p.Pro1131=

c.3393C>T · rs782003334 · VCV2056370

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, 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 -20	GERP -3.7
Overall
CADD	0.871	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0148% East Asian · 5/33,793 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00373%

Overall 0.0033% 40/1,210,596 alleles · ultra-rare exomes 33/1,097,357 · genomes 7/113,239 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0148%	6,759
African / African-American	0.00867%	11,534
South Asian	0.00527%	18,981
Remaining individualsnot grpmax-eligible	0.0042%	23,816
European (non-Finnish)	0.00268%	37,306
Admixed American	0.00217%	46,092

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.Pro1131=
Coding: c.3393C>T
MANE Select: NM_001110556
dbSNP: rs782003334
Type: single nucleotide variant
Location: chrX:154360402 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB

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-pro1131 (accessed [today's date]).

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