Is FLNB p.Val571Met (c.1711G>A) pathogenic?

FLNB p.Val571Met (c.1711G>A) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-20). AlphaMissense: likely benign (0.301); Ultra-rare (popmax 0.0242%, sas).

How common is FLNB p.Val571Met (c.1711G>A) in the general population?

FLNB p.Val571Met (c.1711G>A) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

What do computational predictors say about FLNB p.Val571Met (c.1711G>A)?

AlphaMissense predicts likely benign (score 0.301) — an in-silico prediction, not a clinical call.

FLNB p.Val571Met

c.1711G>A · rs760127618 · VCV1428418

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.301 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.301	likely benign
REVEL	0.638	indeterminate
SaProt	LLR -8.68	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 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	25.2	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 0.0242% South Asian · 22/91,086 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00246% 36/1,461,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,140
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
Admixed American	0.00333%	30,014
Remaining individualsnot grpmax-eligible	0.0032%	31,254
East Asian	0.00223%	44,882
European (non-Finnish)	0.000424%	236,008

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.Val571Met
Coding: c.1711G>A
MANE Select: NM_001457
dbSNP: rs760127618
Type: single nucleotide variant
Location: chr3:58105180 (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

Similar variants

FLNB p.Val571Leu Uncertain significance ★ ⚠ 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
FLNB p.Glu227Lys 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-val571met (accessed [today's date]).

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