Is DNAJA3 p.Trp9Arg (c.25T>A) pathogenic?

DNAJA3 p.Trp9Arg (c.25T>A) is classified Uncertain significance in DNAJA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely pathogenic (0.6029); Very rare (popmax 0.00197%, amr).

How common is DNAJA3 p.Trp9Arg (c.25T>A) in the general population?

DNAJA3 p.Trp9Arg (c.25T>A) is very rare (popmax 0.00197%, amr) (gnomAD).

What do computational predictors say about DNAJA3 p.Trp9Arg (c.25T>A)?

AlphaMissense predicts likely pathogenic (score 0.6029) — an in-silico prediction, not a clinical call.

DNAJA3 p.Trp9Arg

c.25T>A · VCV4243021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00197%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6029	likely pathogenic
REVEL	0.483	indeterminate
SaProt	LLR -6.05	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 29 kb · p 0.0067 · regional, not allelic
Overall
CADD	32.0	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 0.00197% Admixed American · 1/50,854 alleles

Filtering AF 0.000515% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000376%

Overall 0.000862% 12/1,391,900 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00197%	50,854
European (non-Finnish)	0.00096%	104,177

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.Trp9Arg
Coding: c.25T>A
MANE Select: NM_005147
Type: single nucleotide variant
Location: chr16:4425906 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.04 · 4 PDB

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-trp9arg (accessed [today's date]).

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