Is FLNB p.Arg36His (c.107G>A) pathogenic?

FLNB p.Arg36His (c.107G>A) is classified Conflicting classifications of pathogenicity in FLNB (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1399); Rare (popmax 0.819%, afr); Associated with connective tissue disorder.

What condition is associated with FLNB p.Arg36His (c.107G>A)?

FLNB p.Arg36His (c.107G>A) is associated with connective tissue disorder (ClinVar).

How common is FLNB p.Arg36His (c.107G>A) in the general population?

FLNB p.Arg36His (c.107G>A) is rare (popmax 0.819%, afr) (gnomAD).

What do computational predictors say about FLNB p.Arg36His (c.107G>A)?

AlphaMissense predicts likely benign (score 0.1399) — an in-silico prediction, not a clinical call.

FLNB p.Arg36His

c.107G>A · rs142568031 · VCV439738

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1399 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.819%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

connective tissue disorder

Computational evidence

Protein change
AlphaMissense	0.1399	likely benign
REVEL	0.624	indeterminate
SaProt	LLR -5.80	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 9.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 89 kb · p 2.4e-13 · regional, not allelic
Overall
CADD	32.0	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 0.819% African / African-American · 615/75,068 alleles

Filtering AF 0.766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.744%

Overall 0.0418% 675/1,614,156 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.819%	122
Remaining individualsnot grpmax-eligible	0.0528%	1,894
Middle Eastern	0.0495%	2,021
Admixed American	0.0366%	2,729
South Asian	0.0022%	45,544

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.Arg36His
Coding: c.107G>A
MANE Select: NM_001457
dbSNP: rs142568031
Type: single nucleotide variant
Location: chr3:58008671 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.96 · 23 PDB
Residue 36: the calponin-homology (ch) 1 domain; the 'actin-binding' region

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

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNB p.Arg36Leu Uncertain significance ★★ ⚠ same residue
FLNB p.Phe161Cys Likely pathogenic ★★ same condition
FLNB p.Gly496Cys Uncertain significance ★★ ⚠ same condition
FLNB p.Thr1003Met Uncertain significance ★★ ⚠ same condition
FLNB p.Thr1579Ile Uncertain significance ★★ ⚠ same condition
FLNB c.1611-4G>A Benign ★★ same condition
FLNB c.292+8C>A Benign/Likely benign ★★ same condition
FLNB c.4222+8A>G Benign/Likely benign ★★ 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-arg36his (accessed [today's date]).

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