Is DNAJB13 p.Pro284Ser (c.850C>T) pathogenic?

DNAJB13 p.Pro284Ser (c.850C>T) is classified Uncertain significance in DNAJB13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1205); Very rare (popmax 0.00127%, nfe).

How common is DNAJB13 p.Pro284Ser (c.850C>T) in the general population?

DNAJB13 p.Pro284Ser (c.850C>T) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about DNAJB13 p.Pro284Ser (c.850C>T)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

DNAJB13 p.Pro284Ser

c.850C>T · VCV4661262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 4.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 19 kb · p 0.47 · regional, not allelic
Overall
CADD	21.5	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 0.00127% European (non-Finnish) · 15/1,178,760 alleles

Filtering AF 0.000764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.00103% 15/1,459,352 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: DNAJB13
Protein: p.Pro284Ser
Coding: c.850C>T
MANE Select: NM_153614
Type: single nucleotide variant
Location: chr11:73970013 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.81 · 1 PDB

Full DNAJB13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB13 p.Gln136Ter Pathogenic/Likely pathogenic ★★ same type
DNAJB13 p.Arg131Gln Uncertain significance ★★ ⚠ same type
DNAJB13 p.Arg142Gln Uncertain significance ★★ ⚠ same type
DNAJB13 p.Arg222Cys Uncertain significance ★★ ⚠ same type
DNAJB13 p.Arg301Cys Uncertain significance ★★ ⚠ same type
DNAJB13 p.Asn14Asp Uncertain significance ★★ ⚠ same type
DNAJB13 p.Asp169Gly Uncertain significance ★★ ⚠ same type
DNAJB13 p.Asp65Asn 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/dnajb13-p-pro284ser (accessed [today's date]).

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