Is DNAJB2 p.Ser170Phe (c.509C>T) pathogenic?

DNAJB2 p.Ser170Phe (c.509C>T) is classified Uncertain significance in DNAJB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-13). AlphaMissense: likely pathogenic (0.7893); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DNAJB2 p.Ser170Phe (c.509C>T)?

DNAJB2 p.Ser170Phe (c.509C>T) is associated with Inborn genetic diseases, neuronopathy, distal hereditary motor, autosomal recessive 5 (ClinVar).

How common is DNAJB2 p.Ser170Phe (c.509C>T) in the general population?

DNAJB2 p.Ser170Phe (c.509C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJB2 p.Ser170Phe (c.509C>T)?

AlphaMissense predicts likely pathogenic (score 0.7893) — an in-silico prediction, not a clinical call.

DNAJB2 p.Ser170Phe

c.509C>T · rs1951922399 · VCV1394995

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7893 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7893	likely pathogenic
REVEL	0.432	indeterminate
SaProt	LLR -13.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 5,150 bp · p 0.0024 · regional, not allelic
Overall
CADD	29.8	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

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: DNAJB2
Protein: p.Ser170Phe
Coding: c.509C>T
MANE Select: NM_006736
dbSNP: rs1951922399
Type: single nucleotide variant
Location: chr2:219283196 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB

Full DNAJB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronopathy, distal hereditary motor, autosomal recessive 5

Similar variants

DNAJB2 c.175+2T>A Pathogenic/Likely pathogenic ★★ same condition
DNAJB2 c.352+1G>A Pathogenic ★★ same condition
DNAJB2 c.65+1G>A Likely pathogenic ★★ same condition
DNAJB2 p.Arg104Gln Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg165Cys Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg178His Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg182Cys Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg191Gln 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/dnajb2-p-ser170phe (accessed [today's date]).

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