Is DNAJB2 p.Tyr65= (c.195C>T) pathogenic?

DNAJB2 p.Tyr65= (c.195C>T) is classified Benign/Likely benign in DNAJB2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-03-01). Rare (popmax 0.196%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAJB2 p.Tyr65= (c.195C>T)?

DNAJB2 p.Tyr65= (c.195C>T) is associated with Inborn genetic diseases, neuronopathy, distal hereditary motor, autosomal recessive 5, Charcot-Marie-Tooth disease (ClinVar).

How common is DNAJB2 p.Tyr65= (c.195C>T) in the general population?

DNAJB2 p.Tyr65= (c.195C>T) is rare (popmax 0.196%, nfe) (gnomAD).

DNAJB2 p.Tyr65=

c.195C>T · rs116719245 · VCV377779

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.196%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.1	GERP -4.4
Overall
CADD	6.521	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.196% European (non-Finnish) · 2,310/1,180,022 alleles

Filtering AF 0.189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.186%

Overall 0.151% 2,433/1,613,964 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.196%	511
Remaining individualsnot grpmax-eligible	0.0992%	1,008
Admixed American	0.0583%	1,715
African / African-American	0.024%	4,166
Finnishnot grpmax-eligible	0.00939%	10,648
South Asian	0.0022%	45,542

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.Tyr65=
Coding: c.195C>T
MANE Select: NM_006736
dbSNP: rs116719245
Type: single nucleotide variant
Location: chr2:219281737 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB
Residue 65: the j domain; an α-helix

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 Charcot-Marie-Tooth disease

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-tyr65 (accessed [today's date]).

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