Is FLNA p.Val1297= (c.3891G>C) pathogenic?

FLNA p.Val1297= (c.3891G>C) is classified Likely benign in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-23). Absent from gnomAD v4.1; Associated with otopalatodigital syndrome type 2.

What condition is associated with FLNA p.Val1297= (c.3891G>C)?

FLNA p.Val1297= (c.3891G>C) is associated with otopalatodigital syndrome type 2, heterotopia, periventricular, X-linked dominant, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Val1297= (c.3891G>C) in the general population?

FLNA p.Val1297= (c.3891G>C) is absent from gnomAD v4.1 (gnomAD).

FLNA p.Val1297=

c.3891G>C · rs1603360998 · VCV2941711

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.34	GERP -3.4
Overall
CADD	6.873	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLNA
Protein: p.Val1297=
Coding: c.3891G>C
MANE Select: NM_001110556
dbSNP: rs1603360998
Type: single nucleotide variant
Location: chrX:154359820 (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.Val1297fs Likely pathogenic ★ 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-val1297 (accessed [today's date]).

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