Is FLNB p.Ala1719Val (c.5156C>T) pathogenic?

FLNB p.Ala1719Val (c.5156C>T) is classified Uncertain significance in FLNB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: likely benign (0.1286); Very rare (popmax 0.00223%, eas).

How common is FLNB p.Ala1719Val (c.5156C>T) in the general population?

FLNB p.Ala1719Val (c.5156C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about FLNB p.Ala1719Val (c.5156C>T)?

AlphaMissense predicts likely benign (score 0.1286) — an in-silico prediction, not a clinical call.

FLNB p.Ala1719Val

c.5156C>T · VCV3375229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1286 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1286	likely benign
REVEL	0.335	indeterminate
SaProt	LLR -5.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 32 kb · p 1.7e-10 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Overall 6.84e-05% 1/1,461,860 alleles · very rare

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: FLNB
Protein: p.Ala1719Val
Coding: c.5156C>T
MANE Select: NM_001457
Type: single nucleotide variant
Location: chr3:58141904 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1719: the 'hinge 1' region

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

Similar variants

FLNB p.Ala1719= Likely benign ★ same residue
FLNB c.4390+2T>C Pathogenic/Likely pathogenic ★★ same type
FLNB c.5110-1G>A Likely pathogenic ★★ same type
FLNB p.Arg1463Ter Pathogenic/Likely pathogenic ★★ same type
FLNB p.Arg1948Ter Pathogenic ★★ same type
FLNB p.Arg649Ter Pathogenic ★★ same type
FLNB p.Asp167Gly Likely pathogenic ★★ ⚠ same type
FLNB p.Glu227Lys Pathogenic ★★ same type

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-ala1719val (accessed [today's date]).

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