Is FLNB p.Met270Val (c.808A>G) pathogenic?

FLNB p.Met270Val (c.808A>G) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0941); Rare (popmax 0.143%, nfe); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Met270Val (c.808A>G)?

FLNB p.Met270Val (c.808A>G) is associated with FLNB-Related Spectrum Disorders, connective tissue disorder, atelosteogenesis type I (ClinVar).

How common is FLNB p.Met270Val (c.808A>G) in the general population?

FLNB p.Met270Val (c.808A>G) is rare (popmax 0.143%, nfe) (gnomAD).

What do computational predictors say about FLNB p.Met270Val (c.808A>G)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

FLNB p.Met270Val

c.808A>G · rs145036794 · VCV252548

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.143%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FLNB-Related Spectrum Disorders

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -3.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 89 kb · p 2.4e-13 · regional, not allelic
Overall
CADD	23.5	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

Grpmax group 0.143% European (non-Finnish) · 1,683/1,179,980 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.115% 1,864/1,614,128 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.143%	701
Remaining individualsnot grpmax-eligible	0.11%	906
Ashkenazi Jewishnot grpmax-eligible	0.0811%	1,234
Admixed American	0.0616%	1,622
African / African-American	0.0466%	2,144
Finnishnot grpmax-eligible	0.0234%	4,269
Middle Eastern	0.0165%	6,062

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.Met270Val
Coding: c.808A>G
MANE Select: NM_001457
dbSNP: rs145036794
Type: single nucleotide variant
Location: chr3:58094856 (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

FLNB-Related Spectrum Disorders

Also linked: connective tissue disorder 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-met270val (accessed [today's date]).

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