Is FLNB p.Val1435Ile (c.4303G>A) pathogenic?

FLNB p.Val1435Ile (c.4303G>A) is classified Likely benign in FLNB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-12). AlphaMissense: likely benign (0.1184); Ultra-rare (popmax 0.0418%, sas); Associated with Inborn genetic diseases.

What condition is associated with FLNB p.Val1435Ile (c.4303G>A)?

FLNB p.Val1435Ile (c.4303G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FLNB p.Val1435Ile (c.4303G>A) in the general population?

FLNB p.Val1435Ile (c.4303G>A) is ultra-rare (popmax 0.0418%, sas) (gnomAD).

What do computational predictors say about FLNB p.Val1435Ile (c.4303G>A)?

AlphaMissense predicts likely benign (score 0.1184) — an in-silico prediction, not a clinical call.

FLNB p.Val1435Ile

c.4303G>A · rs536769087 · VCV1898156

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1184 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0418%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1184	likely benign
REVEL	0.449	indeterminate
SaProt	LLR -3.27	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 6.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	24.7	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 0.0418% South Asian · 38/90,940 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0276%

Overall 0.00403% 65/1,613,528 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0418%	2,393
African / African-American	0.0134%	7,490
Remaining individualsnot grpmax-eligible	0.0048%	20,819
Admixed American	0.00167%	59,966
Finnishnot grpmax-eligible	0.00156%	64,010
European (non-Finnish)	0.00102%	98,322

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.Val1435Ile
Coding: c.4303G>A
MANE Select: NM_001457
dbSNP: rs536769087
Type: single nucleotide variant
Location: chr3:58130821 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 1435: 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.Val1435Leu Uncertain significance ★★ ⚠ same residue
FLNB p.Val1435= Likely 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.Ala1391Thr Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1427Val Uncertain significance ★★ ⚠ same condition
FLNB p.Ala1608Val 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-val1435ile (accessed [today's date]).

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