Is FBP2 p.Arg255Pro (c.764G>C) pathogenic?

FBP2 p.Arg255Pro (c.764G>C) is classified Uncertain significance in FBP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-08-03). AlphaMissense: likely pathogenic (0.9989); Rare (popmax 0.343%, sas); Associated with leukodystrophy, childhood-onset, remitting.

What condition is associated with FBP2 p.Arg255Pro (c.764G>C)?

FBP2 p.Arg255Pro (c.764G>C) is associated with leukodystrophy, childhood-onset, remitting (ClinVar).

How common is FBP2 p.Arg255Pro (c.764G>C) in the general population?

FBP2 p.Arg255Pro (c.764G>C) is rare (popmax 0.343%, sas) (gnomAD).

What do computational predictors say about FBP2 p.Arg255Pro (c.764G>C)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

FBP2 p.Arg255Pro

c.764G>C · VCV4884782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.343%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

leukodystrophy, childhood-onset, remitting

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic · top 1% in FBP2
REVEL	0.94	strongly pathogenic-leaning
SaProt	LLR -16.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 0.89, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 35 kb · p 0.47 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.343% South Asian · 312/91,052 alleles

Filtering AF 0.311% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.299%

Overall 0.0204% 329/1,613,874 alleles · rare exomes 306/1,461,608 · genomes 23/152,266 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.343%	292
Remaining individualsnot grpmax-eligible	0.0224%	4,464
Middle Eastern	0.0165%	6,062
African / African-American	0.00267%	37,512

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: FBP2
Protein: p.Arg255Pro
Coding: c.764G>C
MANE Select: NM_003837
Type: single nucleotide variant
Location: chr9:94563403 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.87 · 14 PDB
Residue 255: an α-helix

Full FBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

leukodystrophy, childhood-onset, remitting — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FBP2 p.Asp122Asn Uncertain significance ★ ⚠ same condition
FBP2 p.Gly237Asp Uncertain significance ★ ⚠ same condition
FBP2 p.Leu35Pro Uncertain significance ★ ⚠ same condition
FBP2 p.Val115Met Uncertain significance ★ ⚠ same condition
FBP2 p.Ile133Val Uncertain significance ★★ ⚠ same type
FBP2 p.Ser211Asn Benign ★★ same type
FBP2 p.Ter340Trp Benign ★★ same type
FBP2 p.Thr225= Benign ★★ 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/fbp2-p-arg255pro (accessed [today's date]).

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