Is DNAJB6 p.Pro36Ser (c.106C>T) pathogenic?

DNAJB6 p.Pro36Ser (c.106C>T) is classified Uncertain significance in DNAJB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: likely pathogenic (0.9832); Absent from gnomAD v4.1.

How common is DNAJB6 p.Pro36Ser (c.106C>T) in the general population?

DNAJB6 p.Pro36Ser (c.106C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJB6 p.Pro36Ser (c.106C>T)?

AlphaMissense predicts likely pathogenic (score 0.9832) — an in-silico prediction, not a clinical call.

DNAJB6 p.Pro36Ser

c.106C>T · VCV3371152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9832 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9832	likely pathogenic
REVEL	0.563	indeterminate
SaProt	LLR -11.81	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 5.7	GERP 2, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 8,817 bp · p 0.017 · regional, not allelic
Overall
CADD	27.7	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: DNAJB6
Protein: p.Pro36Ser
Coding: c.106C>T
MANE Select: NM_058246
Type: single nucleotide variant
Location: chr7:157363201 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.04 · 4 PDB
Residue 36: the j domain; the 'interaction with hsp70' region

Full DNAJB6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB6 p.Phe89Ile Pathogenic ★★ same type
DNAJB6 p.Phe91Leu Pathogenic ★★ same type
DNAJB6 p.Phe91Val Pathogenic/Likely pathogenic ★★ same type
DNAJB6 p.Pro96Arg Pathogenic ★★ same type
DNAJB6 c.66-2A>G Uncertain significance ★★ same type
DNAJB6 c.-7G>A Uncertain significance ★★ same type
DNAJB6 p.Ala22Val Uncertain significance ★★ ⚠ same type
DNAJB6 p.Ala237Pro Uncertain significance ★★ ⚠ 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/dnajb6-p-pro36ser (accessed [today's date]).

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