Is FLNB p.Pro679Ser (c.2035C>T) pathogenic?

FLNB p.Pro679Ser (c.2035C>T) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-03). AlphaMissense: likely benign (0.097); Ultra-rare (popmax 0.0493%, afr); Associated with FLNB-Related Spectrum Disorders.

What condition is associated with FLNB p.Pro679Ser (c.2035C>T)?

FLNB p.Pro679Ser (c.2035C>T) is associated with FLNB-Related Spectrum Disorders (ClinVar).

How common is FLNB p.Pro679Ser (c.2035C>T) in the general population?

FLNB p.Pro679Ser (c.2035C>T) is ultra-rare (popmax 0.0493%, afr) (gnomAD).

What do computational predictors say about FLNB p.Pro679Ser (c.2035C>T)?

AlphaMissense predicts likely benign (score 0.097) — an in-silico prediction, not a clinical call.

FLNB p.Pro679Ser

c.2035C>T · rs144158201 · VCV346317

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.097 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

FLNB-Related Spectrum Disorders

Computational evidence

Protein change
AlphaMissense	0.097	likely benign
REVEL	0.433	indeterminate
SaProt	LLR -9.30	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 3.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	23.9	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 0.0493% African / African-American · 37/75,008 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0324%

Overall 0.00273% 44/1,613,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0493%	2,027
Middle Eastern	0.0165%	6,046
Remaining individualsnot grpmax-eligible	0.0064%	15,624
European (non-Finnish)	0.00017%	589,543

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.Pro679Ser
Coding: c.2035C>T
MANE Select: NM_001457
dbSNP: rs144158201
Type: single nucleotide variant
Location: chr3:58108551 (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

Disease context

FLNB-Related Spectrum Disorders

Similar variants

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FLNB p.Glu78Gly Uncertain significance ★★ ⚠ same condition
FLNB p.His1117Arg Uncertain significance ★★ ⚠ same condition
FLNB p.Leu1440Pro Uncertain significance ★★ ⚠ same condition
FLNB p.Pro396Ser Uncertain significance ★★ ⚠ same condition
FLNB p.Ser1096Phe Uncertain significance ★★ ⚠ same condition
FLNB p.Ser188Cys Uncertain significance ★★ ⚠ same condition
FLNB p.Tyr63His 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-pro679ser (accessed [today's date]).

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