Is FLNA p.Val570= (c.1710G>A) pathogenic?

FLNA p.Val570= (c.1710G>A) is classified Likely benign in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-19). Very rare (popmax 0.00201%, nfe); Associated with otopalatodigital syndrome type 2.

What condition is associated with FLNA p.Val570= (c.1710G>A)?

FLNA p.Val570= (c.1710G>A) is associated with otopalatodigital syndrome type 2, heterotopia, periventricular, X-linked dominant, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Val570= (c.1710G>A) in the general population?

FLNA p.Val570= (c.1710G>A) is very rare (popmax 0.00201%, nfe) (gnomAD).

FLNA p.Val570=

c.1710G>A · rs376557256 · VCV2942617

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00201%, nfe)

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 -0.028	GERP -0.7, phastCons 0.001
Overall
CADD	11.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00201% European (non-Finnish) · 18/895,287 alleles

Filtering AF 0.00126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00157% 19/1,209,967 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00201%	49,738
African / African-American	0.00174%	57,336

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.Val570=
Coding: c.1710G>A
MANE Select: NM_001110556
dbSNP: rs376557256
Type: single nucleotide variant
Location: chrX:154364939 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 570: a β-strand

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.Val570Leu 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-val570 (accessed [today's date]).

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