Is FLNB p.Ala1517Asp (c.4550C>A) pathogenic?

FLNB p.Ala1517Asp (c.4550C>A) is classified Likely pathogenic in FLNB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). AlphaMissense: likely pathogenic (0.9775); Absent from gnomAD v4.1; Associated with Larsen syndrome.

What condition is associated with FLNB p.Ala1517Asp (c.4550C>A)?

FLNB p.Ala1517Asp (c.4550C>A) is associated with Larsen syndrome (ClinVar).

How common is FLNB p.Ala1517Asp (c.4550C>A) in the general population?

FLNB p.Ala1517Asp (c.4550C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNB p.Ala1517Asp (c.4550C>A)?

AlphaMissense predicts likely pathogenic (score 0.9775) — an in-silico prediction, not a clinical call.

FLNB p.Ala1517Asp

c.4550C>A · rs372940610 · VCV1683442

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9775 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Larsen syndrome

Computational evidence

Protein change
AlphaMissense	0.9775	likely pathogenic ✓ concordant with ClinVar · top 10% in FLNB
REVEL	0.892	moderately pathogenic-leaning
SaProt	LLR -13.22	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 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,301 bp · p 3.3e-05 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

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: FLNB
Protein: p.Ala1517Asp
Coding: c.4550C>A
MANE Select: NM_001457
dbSNP: rs372940610
Type: single nucleotide variant
Location: chr3:58134651 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1517: an α-helix

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

Disease context

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

Similar variants

FLNB p.Glu227Lys Pathogenic ★★ same condition
FLNB p.Gly168Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
FLNB p.Gly1691Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
FLNB p.Gly1691Ser Pathogenic ★★ ⚠ same condition
FLNB p.Gly361Asp Pathogenic ★★ same condition
FLNB p.Phe161Cys Likely pathogenic ★★ same condition
FLNB c.3724+4G>C Uncertain significance ★★ same condition
FLNB p.Ala433Asp 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/flnb-p-ala1517asp (accessed [today's date]).

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