Is DNAJB2 p.Val208Ile (c.622G>A) pathogenic?

DNAJB2 p.Val208Ile (c.622G>A) is classified Conflicting classifications of pathogenicity in DNAJB2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-14). AlphaMissense: likely benign (0.0582); Ultra-rare (popmax 0.0474%, eas); Associated with Inborn genetic diseases.

What condition is associated with DNAJB2 p.Val208Ile (c.622G>A)?

DNAJB2 p.Val208Ile (c.622G>A) is associated with Inborn genetic diseases, neuronopathy, distal hereditary motor, autosomal recessive 5 (ClinVar).

How common is DNAJB2 p.Val208Ile (c.622G>A) in the general population?

DNAJB2 p.Val208Ile (c.622G>A) is ultra-rare (popmax 0.0474%, eas) (gnomAD).

What do computational predictors say about DNAJB2 p.Val208Ile (c.622G>A)?

AlphaMissense predicts likely benign (score 0.0582) — an in-silico prediction, not a clinical call.

DNAJB2 p.Val208Ile

c.622G>A · rs752078357 · VCV1447614

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0582 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0474%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0582	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -7.41	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 1.2	GERP -0.18, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 5,150 bp · p 0.0024 · regional, not allelic
Overall
CADD	18.04	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 0.0474% East Asian · 21/44,348 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0267%

Overall 0.00145% 23/1,582,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0474%	2,112
Remaining individualsnot grpmax-eligible	0.00164%	60,904
European (non-Finnish)	8.62e-05%	1,159,668

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: DNAJB2
Protein: p.Val208Ile
Coding: c.622G>A
MANE Select: NM_006736
dbSNP: rs752078357
Type: single nucleotide variant
Location: chr2:219284634 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB

Full DNAJB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronopathy, distal hereditary motor, autosomal recessive 5

Similar variants

DNAJB2 c.175+2T>A Pathogenic/Likely pathogenic ★★ same condition
DNAJB2 c.352+1G>A Pathogenic ★★ same condition
DNAJB2 c.65+1G>A Likely pathogenic ★★ same condition
DNAJB2 p.Arg104Gln Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg165Cys Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg178His Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg182Cys Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg191Gln Uncertain significance ★★ ⚠ same condition

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/dnajb2-p-val208ile (accessed [today's date]).

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