Is FLNB p.Pro191Thr (c.571C>A) pathogenic?

FLNB p.Pro191Thr (c.571C>A) is classified Uncertain significance in FLNB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-06). AlphaMissense: likely benign (0.0823); Very rare (popmax 0.00446%, eas).

How common is FLNB p.Pro191Thr (c.571C>A) in the general population?

FLNB p.Pro191Thr (c.571C>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about FLNB p.Pro191Thr (c.571C>A)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

FLNB p.Pro191Thr

c.571C>A · rs529273616 · VCV1723673

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.557	indeterminate
SaProt	LLR -8.54	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 3.3	GERP 2.8, 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

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 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,613,902 alleles · very rare

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.Pro191Thr
Coding: c.571C>A
MANE Select: NM_001457
dbSNP: rs529273616
Type: single nucleotide variant
Location: chr3:58078746 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 191: the calponin-homology (ch) 2 domain; the 'actin-binding' region

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

Similar variants

FLNB p.Pro191= Likely benign ★★ same residue
FLNB p.Pro191Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro191thr (accessed [today's date]).

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