Is FLNB p.Ile92Val (c.274A>G) pathogenic?

FLNB p.Ile92Val (c.274A>G) is classified Benign/Likely benign in FLNB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). AlphaMissense: ambiguous (0.4222); Rare (popmax 0.711%, afr).

How common is FLNB p.Ile92Val (c.274A>G) in the general population?

FLNB p.Ile92Val (c.274A>G) is rare (popmax 0.711%, afr) (gnomAD).

What do computational predictors say about FLNB p.Ile92Val (c.274A>G)?

AlphaMissense predicts ambiguous (score 0.4222) — an in-silico prediction, not a clinical call.

FLNB p.Ile92Val

c.274A>G · rs62622011 · VCV506644

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

ambiguous

0.4222 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.711%, afr)

Computational evidence

Protein change
AlphaMissense	0.4222	ambiguous
REVEL	0.54	indeterminate
SaProt	LLR -6.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 89 kb · p 2.4e-13 · 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 0.711% African / African-American · 534/75,060 alleles

Filtering AF 0.661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.642%

Overall 0.0525% 847/1,613,802 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.711%	141
Middle Eastern	0.182%	551
Remaining individualsnot grpmax-eligible	0.0848%	1,179
Admixed American	0.0716%	1,396
European (non-Finnish)	0.0166%	6,020
Finnishnot grpmax-eligible	0.0141%	7,076
South Asian	0.0011%	91,088

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.Ile92Val
Coding: c.274A>G
MANE Select: NM_001457
dbSNP: rs62622011
Type: single nucleotide variant
Location: chr3:58008838 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 92: the calponin-homology (ch) 1 domain; the 'actin-binding' region

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

Similar variants

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
FLNB p.Gly168Ser Pathogenic/Likely 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-ile92val (accessed [today's date]).

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