Is BDNF p.Pro188Arg (c.563C>G) pathogenic?

BDNF p.Pro188Arg (c.563C>G) is classified Uncertain significance in BDNF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.3309); Absent from gnomAD v4.1; Associated with BDNF-related disorder.

What condition is associated with BDNF p.Pro188Arg (c.563C>G)?

BDNF p.Pro188Arg (c.563C>G) is associated with BDNF-related disorder (ClinVar).

How common is BDNF p.Pro188Arg (c.563C>G) in the general population?

BDNF p.Pro188Arg (c.563C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BDNF p.Pro188Arg (c.563C>G)?

AlphaMissense predicts likely benign (score 0.3309) — an in-silico prediction, not a clinical call.

BDNF p.Pro188Arg

c.563C>G · VCV3349325

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3309 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BDNF-related disorder

Computational evidence

Protein change
AlphaMissense	0.3309	likely benign
REVEL	0.491	indeterminate
SaProt	LLR -11.06	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 364 bp · p 6.8e-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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BDNF
Protein: p.Pro188Arg
Coding: c.563C>G
MANE Select: NM_001709
Type: single nucleotide variant
Location: chr11:27658002 (GRCh38)
Gene constraint: LOEUF 0.233 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.44 · 2 PDB
Residue 188: a disulfide bond

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

Disease context

BDNF-related disorder

Similar variants

BDNF c.-21-15487T>G Uncertain significance ★ same condition
BDNF c.-21-15496C>G Uncertain significance ★ same condition
BDNF p.Arg38Gln Uncertain significance ★ ⚠ same condition
BDNF p.Gly31Asp Uncertain significance ★ ⚠ same condition
BDNF p.Lys76Glu Uncertain significance ★ ⚠ same condition
BDNF p.Met220Thr Uncertain significance ★ ⚠ same condition
BDNF c.-21-15481C>A Uncertain significance same condition
BDNF c.-21-15533T>C 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/bdnf-p-pro188arg (accessed [today's date]).

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