Is DNAJC3 p.Pro490His (c.1469C>A) pathogenic?

DNAJC3 p.Pro490His (c.1469C>A) is classified Uncertain significance in DNAJC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: ambiguous (0.5483); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with DNAJC3 p.Pro490His (c.1469C>A)?

DNAJC3 p.Pro490His (c.1469C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJC3 p.Pro490His (c.1469C>A) in the general population?

DNAJC3 p.Pro490His (c.1469C>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DNAJC3 p.Pro490His (c.1469C>A)?

AlphaMissense predicts ambiguous (score 0.5483) — an in-silico prediction, not a clinical call.

DNAJC3 p.Pro490His

c.1469C>A · rs775095589 · VCV2528464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5483 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5483	ambiguous
REVEL	0.19	benign-leaning
SaProt	LLR -7.10	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 114 kb · p 0.0067 · regional, not allelic
Overall
CADD	23.7	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 0.00446% East Asian · 2/44,838 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000137% 2/1,461,334 alleles · very rare

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.Pro490His
Coding: c.1469C>A
MANE Select: NM_006260
dbSNP: rs775095589
Type: single nucleotide variant
Location: chr13:95790984 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.78 · 2 PDB

Full DNAJC3 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

Similar variants

DNAJC3 p.Leu231Val Uncertain significance ★★ ⚠ same condition
DNAJC3 p.Thr171Ile Uncertain significance ★★ ⚠ same condition
DNAJC3 p.Ala164Ser Uncertain significance ★ ⚠ same condition
DNAJC3 p.Ala224Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
DNAJC3 p.Ala325Thr Uncertain significance ★ ⚠ same condition
DNAJC3 p.Ala366Gly Uncertain significance ★ ⚠ same condition
DNAJC3 p.Arg10Gln Uncertain significance ★ ⚠ same condition
DNAJC3 p.Arg156Cys 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/dnajc3-p-pro490his (accessed [today's date]).

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