Is DNAJA3 p.Gln153Arg (c.458A>G) pathogenic?

DNAJA3 p.Gln153Arg (c.458A>G) is classified Uncertain significance in DNAJA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: ambiguous (0.3744); Very rare (popmax 0.000508%, nfe).

How common is DNAJA3 p.Gln153Arg (c.458A>G) in the general population?

DNAJA3 p.Gln153Arg (c.458A>G) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about DNAJA3 p.Gln153Arg (c.458A>G)?

AlphaMissense predicts ambiguous (score 0.3744) — an in-silico prediction, not a clinical call.

DNAJA3 p.Gln153Arg

c.458A>G · rs148624679 · VCV2310880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3744 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3744	ambiguous
REVEL	0.368	indeterminate
SaProt	LLR -8.22	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 29 kb · p 0.0067 · regional, not allelic
Overall
CADD	25.4	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 0.000508% European (non-Finnish) · 6/1,179,998 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,726 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: DNAJA3
Protein: p.Gln153Arg
Coding: c.458A>G
MANE Select: NM_005147
dbSNP: rs148624679
Type: single nucleotide variant
Location: chr16:4441403 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.04 · 4 PDB
Residue 153: the j domain; an α-helix

Full DNAJA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJA3 p.Ala112Val Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala21Thr Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala344Thr Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala355Val Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala357Thr Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala365Thr Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala3Val Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala455Thr 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/dnaja3-p-gln153arg (accessed [today's date]).

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