Is DNAJC19 p.Glu111Gln (c.331G>C) pathogenic?

DNAJC19 p.Glu111Gln (c.331G>C) is classified Conflicting classifications of pathogenicity in DNAJC19 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-07-24). AlphaMissense: likely pathogenic (0.7061); Ultra-rare (popmax 0.0962%, afr); Associated with Inborn genetic diseases.

What condition is associated with DNAJC19 p.Glu111Gln (c.331G>C)?

DNAJC19 p.Glu111Gln (c.331G>C) is associated with Inborn genetic diseases, 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 p.Glu111Gln (c.331G>C) in the general population?

DNAJC19 p.Glu111Gln (c.331G>C) is ultra-rare (popmax 0.0962%, afr) (gnomAD).

What do computational predictors say about DNAJC19 p.Glu111Gln (c.331G>C)?

AlphaMissense predicts likely pathogenic (score 0.7061) — an in-silico prediction, not a clinical call.

DNAJC19 p.Glu111Gln

c.331G>C · rs370042988 · VCV1493559

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7061 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0962%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7061	likely pathogenic
REVEL	0.123	moderately benign-leaning
SaProt	LLR -10.52	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 4,959 bp · p 0.0025 · regional, not allelic
Overall
CADD	24.7	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 0.0962% African / African-American · 72/74,830 alleles

Filtering AF 0.0783% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0717%

Overall 0.00522% 84/1,607,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0962%	1,039
Remaining individualsnot grpmax-eligible	0.00965%	10,366
South Asian	0.00442%	22,631
European (non-Finnish)	0.00017%	588,000

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: DNAJC19
Protein: p.Glu111Gln
Coding: c.331G>C
MANE Select: NM_145261
dbSNP: rs370042988
Type: single nucleotide variant
Location: chr3:180984660 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50
Residue 111: the j domain

Full DNAJC19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 3-methylglutaconic aciduria type 5

Similar variants

DNAJC19 p.Glu111Ala Uncertain significance ★ ⚠ same residue
DNAJC19 p.Glu111Lys Uncertain significance ★ ⚠ same residue
DNAJC19 p.Glu111= Likely benign ★ same residue
DNAJC19 c.130-1G>C Pathogenic ★★ same condition
DNAJC19 c.4-1G>A Likely pathogenic ★★ same condition
DNAJC19 c.55+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAJC19 p.Ala25Thr Uncertain significance ★★ ⚠ same condition
DNAJC19 p.Ala73Thr Uncertain significance ★★ ⚠ same condition

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/dnajc19-p-glu111gln (accessed [today's date]).

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