Is DNAJA2 p.Asp222Gly (c.665A>G) pathogenic?

DNAJA2 p.Asp222Gly (c.665A>G) is classified Uncertain significance in DNAJA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely pathogenic (0.9609); Absent from gnomAD v4.1.

How common is DNAJA2 p.Asp222Gly (c.665A>G) in the general population?

DNAJA2 p.Asp222Gly (c.665A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJA2 p.Asp222Gly (c.665A>G)?

AlphaMissense predicts likely pathogenic (score 0.9609) — an in-silico prediction, not a clinical call.

DNAJA2 p.Asp222Gly

c.665A>G · rs2549001537 · VCV3084360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9609 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9609	likely pathogenic
REVEL	0.629	indeterminate
SaProt	LLR -9.51	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 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 17 kb · p 8e-14 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAJA2
Protein: p.Asp222Gly
Coding: c.665A>G
MANE Select: NM_005880
dbSNP: rs2549001537
Type: single nucleotide variant
Location: chr16:46964720 (GRCh38)
Gene constraint: LOEUF 0.258 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 1 PDB

Full DNAJA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJA2 p.Gly79Ser Uncertain significance ★★ ⚠ same type
DNAJA2 p.Arg107Gln Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg110Gly Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg112Gly Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg165Gln Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg201Ser Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg388His Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg68Lys 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/dnaja2-p-asp222gly (accessed [today's date]).

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