Is FLNB p.Val795Met (c.2383G>A) pathogenic?

FLNB p.Val795Met (c.2383G>A) is classified Uncertain significance in FLNB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-10). AlphaMissense: likely benign (0.2398); Very rare (popmax 0.00445%, eas); Associated with Inborn genetic diseases.

What condition is associated with FLNB p.Val795Met (c.2383G>A)?

FLNB p.Val795Met (c.2383G>A) is associated with Inborn genetic diseases, atelosteogenesis type I, atelosteogenesis type III (ClinVar).

How common is FLNB p.Val795Met (c.2383G>A) in the general population?

FLNB p.Val795Met (c.2383G>A) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about FLNB p.Val795Met (c.2383G>A)?

AlphaMissense predicts likely benign (score 0.2398) — an in-silico prediction, not a clinical call.

FLNB p.Val795Met

c.2383G>A · rs145413791 · VCV1903856

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2398 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2398	likely benign
REVEL	0.514	indeterminate
SaProt	LLR -9.55	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 5.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	26.8	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 0.00445% East Asian · 2/44,898 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00217% 35/1,614,000 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,449
European (non-Finnish)	0.00271%	36,875
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Val795Met
Coding: c.2383G>A
MANE Select: NM_001457
dbSNP: rs145413791
Type: single nucleotide variant
Location: chr3:58110069 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atelosteogenesis type I atelosteogenesis type III Boomerang dysplasia Larsen syndrome spondylocarpotarsal synostosis syndrome

Similar variants

FLNB p.Arg1948Ter Pathogenic ★★ same condition
FLNB p.Arg649Ter Pathogenic ★★ same condition
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

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-val795met (accessed [today's date]).

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