Is BDNF p.Ser58Pro (c.172T>C) pathogenic?

BDNF p.Ser58Pro (c.172T>C) is classified Uncertain significance in BDNF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-10). AlphaMissense: likely benign (0.1308); Absent from gnomAD v4.1.

How common is BDNF p.Ser58Pro (c.172T>C) in the general population?

BDNF p.Ser58Pro (c.172T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BDNF p.Ser58Pro (c.172T>C)?

AlphaMissense predicts likely benign (score 0.1308) — an in-silico prediction, not a clinical call.

BDNF p.Ser58Pro

c.172T>C · rs2538964283 · VCV2961667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1308 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1308	likely benign
REVEL	0.365	indeterminate
SaProt	LLR -6.79	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 4.4	GERP -1.6, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 375 bp · p 0.013 · regional, not allelic
Overall
CADD	14.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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.Ser58Pro
Coding: c.172T>C
MANE Select: NM_001709
dbSNP: rs2538964283
Type: single nucleotide variant
Location: chr11:27658393 (GRCh38)
Gene constraint: LOEUF 0.233 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.44 · 2 PDB
Residue 58: a functional site (cleavage; by mbtps1)

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

Similar variants

BDNF c.-21-1044G>C Benign ★★ same type
BDNF c.-21-1065G>A Benign ★★ same type
BDNF c.-21-15778G>T Benign ★★ same type
BDNF c.-22+774G>A Benign ★★ same type
BDNF p.Ala150= Benign ★★ same type
BDNF p.Asp86= Likely benign ★★ same type
BDNF p.Gly161= Likely benign ★★ same type
BDNF p.Thr149= Likely 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/bdnf-p-ser58pro (accessed [today's date]).

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