Is DNAJC3 p.Arg346= (c.1036C>A) pathogenic?

DNAJC3 p.Arg346= (c.1036C>A) is classified Likely benign in DNAJC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-18). Very rare (popmax 0.0011%, sas).

How common is DNAJC3 p.Arg346= (c.1036C>A) in the general population?

DNAJC3 p.Arg346= (c.1036C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

DNAJC3 p.Arg346=

c.1036C>A · rs1594013989 · VCV708443

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.8, phastCons 1
Overall
CADD	13.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,060 alleles

Overall 6.84e-05% 1/1,461,732 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.Arg346=
Coding: c.1036C>A
MANE Select: NM_006260
dbSNP: rs1594013989
Type: single nucleotide variant
Location: chr13:95763914 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.78 · 2 PDB
Residue 346: an α-helix

Full DNAJC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC3 p.Arg346Gln Uncertain significance ★ ⚠ same residue
DNAJC3 p.Arg346Ter Pathogenic same residue
DNAJC3 p.Arg393Ter Pathogenic/Likely pathogenic ★★ same type
DNAJC3 p.Asp69Gly Uncertain significance ★★ ⚠ same type
DNAJC3 p.Leu231Val Uncertain significance ★★ ⚠ same type
DNAJC3 p.Ser450Cys Uncertain significance ★★ ⚠ same type
DNAJC3 p.Thr171Ile Uncertain significance ★★ ⚠ same type
DNAJC3 c.848+10T>C Benign ★★ 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/dnajc3-p-arg346 (accessed [today's date]).

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