Is FLNA p.Ala15Ser (c.43G>T) pathogenic?

FLNA p.Ala15Ser (c.43G>T) is classified Uncertain significance in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). AlphaMissense: likely benign (0.0752); Absent from gnomAD v4.1; Associated with otopalatodigital syndrome type 2.

What condition is associated with FLNA p.Ala15Ser (c.43G>T)?

FLNA p.Ala15Ser (c.43G>T) is associated with otopalatodigital syndrome type 2, heterotopia, periventricular, X-linked dominant, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Ala15Ser (c.43G>T) in the general population?

FLNA p.Ala15Ser (c.43G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNA p.Ala15Ser (c.43G>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

FLNA p.Ala15Ser

c.43G>T · rs782034946 · VCV2925002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,197,215)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

otopalatodigital syndrome type 2

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP 1.3, phastCons 0.02
Regional constraint	o/e 2.09	unconstrained · MANE · 79 bp · p 1e-08 · regional, not allelic
Overall
CADD	19.82	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,197,215). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FLNA
Protein: p.Ala15Ser
Coding: c.43G>T
MANE Select: NM_001110556
dbSNP: rs782034946
Type: single nucleotide variant
Location: chrX:154371203 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 15: the 'disordered' region; 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

Similar variants

FLNA p.Ala15Glu Uncertain significance ★★ ⚠ same residue
FLNA p.Ala15= Likely benign ★★ same residue
FLNA p.Ala15Thr Likely benign ★ 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

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-ala15ser (accessed [today's date]).

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