Is DNAJC2 p.Glu545Ala (c.1634A>C) pathogenic?

DNAJC2 p.Glu545Ala (c.1634A>C) is classified Uncertain significance in DNAJC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.2139); Absent from gnomAD v4.1.

How common is DNAJC2 p.Glu545Ala (c.1634A>C) in the general population?

DNAJC2 p.Glu545Ala (c.1634A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJC2 p.Glu545Ala (c.1634A>C)?

AlphaMissense predicts likely benign (score 0.2139) — an in-silico prediction, not a clinical call.

DNAJC2 p.Glu545Ala

c.1634A>C · rs1818015082 · VCV3084539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2139 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2139	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.86 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 7,271 bp · p 0.069 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: DNAJC2
Protein: p.Glu545Ala
Coding: c.1634A>C
MANE Select: NM_014377
dbSNP: rs1818015082
Type: single nucleotide variant
Location: chr7:103315766 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.51 · 2 PDB

Full DNAJC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC2 c.331+1G>A Uncertain significance ★ same type
DNAJC2 p.Ala308Thr Uncertain significance ★ ⚠ same type
DNAJC2 p.Ala436Gly Uncertain significance ★ ⚠ same type
DNAJC2 p.Ala48Thr Uncertain significance ★ ⚠ same type
DNAJC2 p.Ala616Thr Uncertain significance ★ ⚠ same type
DNAJC2 p.Arg105Gly Uncertain significance ★ ⚠ same type
DNAJC2 p.Arg303Gln Uncertain significance ★ ⚠ same type
DNAJC2 p.Arg321Gln 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/dnajc2-p-glu545ala (accessed [today's date]).

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