Is DNAJB8 p.Arg94Cys (c.280C>T) pathogenic?

DNAJB8 p.Arg94Cys (c.280C>T) is classified Uncertain significance in DNAJB8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-04). AlphaMissense: ambiguous (0.4679); Ultra-rare (popmax 0.0416%, amr).

How common is DNAJB8 p.Arg94Cys (c.280C>T) in the general population?

DNAJB8 p.Arg94Cys (c.280C>T) is ultra-rare (popmax 0.0416%, amr) (gnomAD).

What do computational predictors say about DNAJB8 p.Arg94Cys (c.280C>T)?

AlphaMissense predicts ambiguous (score 0.4679) — an in-silico prediction, not a clinical call.

DNAJB8 p.Arg94Cys

c.280C>T · rs367931490 · VCV2351497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4679 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0416%, amr)

Computational evidence

Protein change
AlphaMissense	0.4679	ambiguous
REVEL	0.562	indeterminate
SaProt	LLR -10.94	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.9, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 695 bp · p 0.049 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0416% Admixed American · 25/60,024 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00613% 99/1,614,148 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0416%	2,401
East Asian	0.0201%	4,986
Middle Eastern	0.0165%	6,062
South Asian	0.00988%	10,120
African / African-American	0.00533%	18,767
European (non-Finnish)	0.00415%	24,081
Remaining individualsnot grpmax-eligible	0.0032%	31,256

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: DNAJB8
Protein: p.Arg94Cys
Coding: c.280C>T
MANE Select: NM_153330
dbSNP: rs367931490
Type: single nucleotide variant
Location: chr3:128462966 (GRCh38)
Gene constraint: LOEUF 1.786 · pLI 0.38 (gnomAD)
Structure: AlphaFold pLDDT 66.35 · 2 PDB

Full DNAJB8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB8 p.Glu6= Benign ★★ same type
DNAJB8 p.Met153Leu Benign ★★ same type
DNAJB8 p.Ala143Asp Uncertain significance ★ ⚠ same type
DNAJB8 p.Ala143Gly Uncertain significance ★ ⚠ same type
DNAJB8 p.Ala147Val Uncertain significance ★ ⚠ same type
DNAJB8 p.Ala68Thr Uncertain significance ★ ⚠ same type
DNAJB8 p.Arg131Ser Uncertain significance ★ ⚠ same type
DNAJB8 p.Arg206His 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/dnajb8-p-arg94cys (accessed [today's date]).

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