Is DNAJC3 p.Asp441Glu (c.1323T>A) pathogenic?

DNAJC3 p.Asp441Glu (c.1323T>A) is classified Likely benign in DNAJC3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-21). AlphaMissense: ambiguous (0.5603); Rare (popmax 0.214%, eas); Associated with DNAJC3-related disorder.

What condition is associated with DNAJC3 p.Asp441Glu (c.1323T>A)?

DNAJC3 p.Asp441Glu (c.1323T>A) is associated with DNAJC3-related disorder (ClinVar).

How common is DNAJC3 p.Asp441Glu (c.1323T>A) in the general population?

DNAJC3 p.Asp441Glu (c.1323T>A) is rare (popmax 0.214%, eas) (gnomAD).

What do computational predictors say about DNAJC3 p.Asp441Glu (c.1323T>A)?

AlphaMissense predicts ambiguous (score 0.5603) — an in-silico prediction, not a clinical call.

DNAJC3 p.Asp441Glu

c.1323T>A · rs185832840 · VCV3051786

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5603 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.214%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

DNAJC3-related disorder

Computational evidence

Protein change
AlphaMissense	0.5603	ambiguous
REVEL	0.258	benign-leaning
SaProt	LLR -7.84	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.091	GERP -1.7, phastCons 0.51
Regional constraint	o/e 0.89	unconstrained · MANE · 114 kb · p 0.0067 · regional, not allelic
Overall
CADD	19.06	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 0.214% East Asian · 96/44,878 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.166%

Overall 0.00645% 104/1,613,352 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.214%	467
Remaining individualsnot grpmax-eligible	0.0128%	7,806

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: DNAJC3
Protein: p.Asp441Glu
Coding: c.1323T>A
MANE Select: NM_006260
dbSNP: rs185832840
Type: single nucleotide variant
Location: chr13:95787121 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.78 · 2 PDB
Residue 441: the j domain; an α-helix

Full DNAJC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNAJC3-related disorder

Similar variants

DNAJC3 p.Arg393Ter Pathogenic/Likely pathogenic ★★ same condition
DNAJC3 c.729-3C>T Likely benign same condition
DNAJC3 p.Asp466= Likely benign same condition
DNAJC3 p.Val37= Likely benign same condition
DNAJC3 p.Asp69Gly Uncertain significance ★★ ⚠ same type
DNAJC3 p.Leu231Val Uncertain significance ★★ ⚠ same type
DNAJC3 p.Ser450Cys Uncertain significance ★★ ⚠ same type
DNAJC3 p.Thr171Ile 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/dnajc3-p-asp441glu (accessed [today's date]).

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