Is FLNA p.Asp1970= (c.5910C>T) pathogenic?

FLNA p.Asp1970= (c.5910C>T) is classified Likely benign in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-29). Ultra-rare (popmax 0.023%, mid); Associated with otopalatodigital syndrome type 2.

What condition is associated with FLNA p.Asp1970= (c.5910C>T)?

FLNA p.Asp1970= (c.5910C>T) is associated with otopalatodigital syndrome type 2, heterotopia, periventricular, X-linked dominant, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Asp1970= (c.5910C>T) in the general population?

FLNA p.Asp1970= (c.5910C>T) is ultra-rare (popmax 0.023%, mid) (gnomAD).

FLNA p.Asp1970=

c.5910C>T · rs2067637398 · VCV2927015

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

Conditions

otopalatodigital syndrome type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.07	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.43	GERP 0.76
Overall
CADD	7.999	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.023% Middle Eastern · 1/4,355 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000413% 5/1,211,795 alleles · ultra-rare exomes 5/1,097,571 · genomes 0/114,224 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.023%	4,355
European (non-Finnish)	0.000447%	223,878

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.Asp1970=
Coding: c.5910C>T
MANE Select: NM_001110556
dbSNP: rs2067637398
Type: single nucleotide variant
Location: chrX:154353408 (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

Similar variants

FLNA p.Asp1970Asn Benign/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
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-asp1970 (accessed [today's date]).

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