Is DNAJB2 p.Ser109Ile (c.326G>T) pathogenic?

DNAJB2 p.Ser109Ile (c.326G>T) is classified Uncertain significance in DNAJB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-25). AlphaMissense: likely benign (0.2901); Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAJB2 p.Ser109Ile (c.326G>T)?

DNAJB2 p.Ser109Ile (c.326G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJB2 p.Ser109Ile (c.326G>T) in the general population?

DNAJB2 p.Ser109Ile (c.326G>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DNAJB2 p.Ser109Ile (c.326G>T)?

AlphaMissense predicts likely benign (score 0.2901) — an in-silico prediction, not a clinical call.

DNAJB2 p.Ser109Ile

c.326G>T · rs2545030150 · VCV2478990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2901 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2901	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -9.54	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 3.3	GERP 0.13, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 5,150 bp · p 0.0024 · regional, not allelic
Overall
CADD	22.7	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

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,050 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,872 alleles · very rare

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: DNAJB2
Protein: p.Ser109Ile
Coding: c.326G>T
MANE Select: NM_006736
dbSNP: rs2545030150
Type: single nucleotide variant
Location: chr2:219282035 (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

Similar variants

DNAJB2 p.Arg178His Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg191Trp Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Asp248Asn Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Asp66Asn Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Gln224Pro Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Pro225Leu Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Ser152Cys Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Ser170Phe 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-ser109ile (accessed [today's date]).

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