Is DNAJB8 p.Arg29His (c.86G>A) pathogenic?

DNAJB8 p.Arg29His (c.86G>A) is classified Uncertain significance in DNAJB8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-18). AlphaMissense: likely benign (0.138); Ultra-rare (popmax 0.015%, amr).

How common is DNAJB8 p.Arg29His (c.86G>A) in the general population?

DNAJB8 p.Arg29His (c.86G>A) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about DNAJB8 p.Arg29His (c.86G>A)?

AlphaMissense predicts likely benign (score 0.138) — an in-silico prediction, not a clinical call.

DNAJB8 p.Arg29His

c.86G>A · VCV3841466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.138 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.138	likely benign
REVEL	0.455	indeterminate
SaProt	LLR -8.45	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 3.9	GERP -0.33, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 695 bp · p 0.049 · regional, not allelic
Overall
CADD	29.6	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 0.015% Admixed American · 9/60,008 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00527% 85/1,614,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,668
European (non-Finnish)	0.00593%	16,858
African / African-American	0.00534%	18,733
Remaining individualsnot grpmax-eligible	0.0016%	62,490
South Asian	0.0011%	91,086

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.Arg29His
Coding: c.86G>A
MANE Select: NM_153330
Type: single nucleotide variant
Location: chr3:128463160 (GRCh38)
Gene constraint: LOEUF 1.786 · pLI 0.38 (gnomAD)
Structure: AlphaFold pLDDT 66.35 · 2 PDB
Residue 29: the j domain; an α-helix

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-arg29his (accessed [today's date]).

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