Is DNAJB5 p.Arg236His (c.707G>A) pathogenic?

DNAJB5 p.Arg236His (c.707G>A) is classified Uncertain significance in DNAJB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.1862); Very rare (popmax 0.00223%, eas).

How common is DNAJB5 p.Arg236His (c.707G>A) in the general population?

DNAJB5 p.Arg236His (c.707G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DNAJB5 p.Arg236His (c.707G>A)?

AlphaMissense predicts likely benign (score 0.1862) — an in-silico prediction, not a clinical call.

DNAJB5 p.Arg236His

c.707G>A · VCV4013532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1862 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1862	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -6.64	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 8.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 3,966 bp · p 2.3e-20 · regional, not allelic
Overall
CADD	25.5	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R164H vs ClinVar R236H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,872 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.0018% 29/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,872
European (non-Finnish)	0.0022%	45,385
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00133%	74,920

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: DNAJB5
Protein: p.Arg236His
Coding: c.707G>A
MANE Select: NM_001349723
Type: single nucleotide variant
Location: chr9:34996544 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 80.69

Full DNAJB5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB5 p.Arg277His Uncertain significance ★★ ⚠ same type
DNAJB5 p.Glu141= Uncertain significance ★★ same type
DNAJB5 p.Thr406Pro Uncertain significance ★★ ⚠ same type
DNAJB5 c.40G>A Uncertain significance ★ same type
DNAJB5 c.50T>C Uncertain significance ★ same type
DNAJB5 c.55G>C Uncertain significance ★ same type
DNAJB5 c.58C>T Uncertain significance ★ same type
DNAJB5 c.-133+6G>A 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/dnajb5-p-arg236his (accessed [today's date]).

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