Is DNAJC2 p.Thr440= (c.1320A>G) pathogenic?

DNAJC2 p.Thr440= (c.1320A>G) is classified Benign in DNAJC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-01). Low-frequency (popmax 1.04%, nfe).

How common is DNAJC2 p.Thr440= (c.1320A>G) in the general population?

DNAJC2 p.Thr440= (c.1320A>G) is low-frequency (popmax 1.04%, nfe) (gnomAD).

DNAJC2 p.Thr440=

c.1320A>G · rs61762984 · VCV2673124

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.04%, nfe)

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 -0.059	GERP -3.7, phastCons 0.75
Overall
CADD	5.887	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.04% European (non-Finnish) · 12,220/1,179,930 alleles

Filtering AF 1.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.01%

Overall 0.919% 14,831/1,614,034 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.83%	35
European (non-Finnish)grpmax	1.04%	97
Remaining individualsnot grpmax-eligible	0.704%	142
Amishnot grpmax-eligible	0.439%	228
African / African-American	0.172%	582
Admixed American	0.155%	645
Ashkenazi Jewishnot grpmax-eligible	0.149%	673
South Asian	0.0933%	1,072
Middle Eastern	0.066%	1,516

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DNAJC2
Protein: p.Thr440=
Coding: c.1320A>G
MANE Select: NM_014377
dbSNP: rs61762984
Type: single nucleotide variant
Location: chr7:103316937 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.51 · 2 PDB
Residue 440: the 'disordered' region

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-thr440 (accessed [today's date]).

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