Is FLNB p.Ala1391Val (c.4172C>T) pathogenic?

FLNB p.Ala1391Val (c.4172C>T) is classified Likely benign in FLNB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-26). AlphaMissense: likely benign (0.0763); Rare (popmax 0.205%, eas); Associated with Inborn genetic diseases.

What condition is associated with FLNB p.Ala1391Val (c.4172C>T)?

FLNB p.Ala1391Val (c.4172C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FLNB p.Ala1391Val (c.4172C>T) in the general population?

FLNB p.Ala1391Val (c.4172C>T) is rare (popmax 0.205%, eas) (gnomAD).

What do computational predictors say about FLNB p.Ala1391Val (c.4172C>T)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

FLNB p.Ala1391Val

c.4172C>T · rs151002497 · VCV1139336

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.205%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -6.98	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 1.7	GERP 2.7, phastCons 0.92
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	19.67	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 0.205% East Asian · 92/44,886 alleles

Filtering AF 0.171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.158%

Overall 0.0165% 266/1,613,814 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.205%	488
Remaining individualsnot grpmax-eligible	0.0352%	2,840
Middle Eastern	0.0329%	3,038
African / African-American	0.0214%	4,680
Admixed American	0.0167%	5,998
Finnishnot grpmax-eligible	0.0125%	8,003
European (non-Finnish)	0.00932%	10,726
South Asian	0.00659%	15,178

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.Ala1391Val
Coding: c.4172C>T
MANE Select: NM_001457
dbSNP: rs151002497
Type: single nucleotide variant
Location: chr3:58126712 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1391: the 'interaction with fblp1' region

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

Similar variants

FLNB p.Ala1391Thr Uncertain significance ★★ ⚠ same residue
FLNB p.Ala1391= Benign ★★ same residue
FLNB c.4862-3C>T Uncertain significance ★★ same condition
FLNB p.Ala1191Thr Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1191Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1427Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1608Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1704Ser 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-ala1391val (accessed [today's date]).

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