Is FLNA p.Ser1630Phe (c.4889C>T) pathogenic?

FLNA p.Ser1630Phe (c.4889C>T) is classified Uncertain significance in FLNA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-06). AlphaMissense: likely pathogenic (0.9947); Absent from gnomAD v4.1; Associated with otopalatodigital syndrome type 1.

What condition is associated with FLNA p.Ser1630Phe (c.4889C>T)?

FLNA p.Ser1630Phe (c.4889C>T) is associated with otopalatodigital syndrome type 1 (ClinVar).

How common is FLNA p.Ser1630Phe (c.4889C>T) in the general population?

FLNA p.Ser1630Phe (c.4889C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNA p.Ser1630Phe (c.4889C>T)?

AlphaMissense predicts likely pathogenic (score 0.9947) — an in-silico prediction, not a clinical call.

FLNA p.Ser1630Phe

c.4889C>T · rs2522733358 · VCV2441467

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9947 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

otopalatodigital syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.9947	likely pathogenic · top 7% in FLNA
REVEL	0.953	strongly pathogenic-leaning
SaProt	LLR -12.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 3.1e-20 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Ser1630Phe
Coding: c.4889C>T
MANE Select: NM_001110556
dbSNP: rs2522733358
Type: single nucleotide variant
Location: chrX:154357490 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 1630: a modified residue (phosphoserine)

Full FLNA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

otopalatodigital syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNA c.4598+1G>A Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Pro207Leu Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Ser1199Leu Pathogenic/Likely pathogenic ★★ same condition
FLNA c.4474+3G>T Uncertain significance ★★ same condition
FLNA p.Asn931Ile Uncertain significance ★★ same condition
FLNA p.Cys1122Gly Uncertain significance ★★ ⚠ same condition
FLNA p.Glu1577Gly Uncertain significance ★★ same condition
FLNA p.Gly524Glu Uncertain significance ★★ ⚠ 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-ser1630phe (accessed [today's date]).

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