Is DNAJC5 p.Arg36Trp (c.106C>T) pathogenic?

DNAJC5 p.Arg36Trp (c.106C>T) is classified Uncertain significance in DNAJC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-12). AlphaMissense: likely pathogenic (0.9981); Very rare (popmax 0.00133%, afr).

How common is DNAJC5 p.Arg36Trp (c.106C>T) in the general population?

DNAJC5 p.Arg36Trp (c.106C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DNAJC5 p.Arg36Trp (c.106C>T)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

DNAJC5 p.Arg36Trp

c.106C>T · rs946559411 · VCV1314672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic · top 10% in DNAJC5
REVEL	0.542	indeterminate
SaProt	LLR -13.61	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.57, phastCons 0.97
Regional constraint	o/e 0.72	unconstrained · MANE · 1,095 bp · p 0.0039 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00133% African / African-American · 1/74,918 alleles

Overall 0.000124% 2/1,613,392 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,918
European (non-Finnish)	8.48e-05%	1,179,572

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: DNAJC5
Protein: p.Arg36Trp
Coding: c.106C>T
MANE Select: NM_025219
dbSNP: rs946559411
Type: single nucleotide variant
Location: chr20:63928451 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 36: the j domain; an α-helix

Full DNAJC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC5 p.Arg36Gln Uncertain significance ★★ ⚠ same residue
DNAJC5 p.Arg36Pro Uncertain significance ★★ ⚠ same residue
DNAJC5 p.Arg36= Uncertain significance ★ same residue
DNAJC5 p.Leu115Arg Pathogenic ★★ same type
DNAJC5 c.-109A>G Uncertain significance ★★ same type
DNAJC5 c.-11-2A>G Uncertain significance ★★ same type
DNAJC5 p.Ala176Val Uncertain significance ★★ ⚠ same type
DNAJC5 p.Ala26Thr 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/dnajc5-p-arg36trp (accessed [today's date]).

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