Is DNAJC19 p.Gly68Ser (c.202G>A) pathogenic?

DNAJC19 p.Gly68Ser (c.202G>A) is classified Uncertain significance in DNAJC19 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-31). AlphaMissense: likely pathogenic (0.7808); Ultra-rare (popmax 0.045%, amr); Associated with Inborn genetic diseases.

What condition is associated with DNAJC19 p.Gly68Ser (c.202G>A)?

DNAJC19 p.Gly68Ser (c.202G>A) is associated with Inborn genetic diseases, 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 p.Gly68Ser (c.202G>A) in the general population?

DNAJC19 p.Gly68Ser (c.202G>A) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about DNAJC19 p.Gly68Ser (c.202G>A)?

AlphaMissense predicts likely pathogenic (score 0.7808) — an in-silico prediction, not a clinical call.

DNAJC19 p.Gly68Ser

c.202G>A · rs754317673 · VCV1474649

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7808 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7808	likely pathogenic
REVEL	0.195	benign-leaning
SaProt	LLR -12.66	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.29 · evaluated, not missing
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	26.1	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 0.045% Admixed American · 27/60,004 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00217% 35/1,613,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,222
South Asian	0.00769%	13,010
Remaining individualsnot grpmax-eligible	0.0016%	62,440

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.Gly68Ser
Coding: c.202G>A
MANE Select: NM_145261
dbSNP: rs754317673
Type: single nucleotide variant
Location: chr3:180986950 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50
Residue 68: 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.Gly68Asp Uncertain significance ★★ ⚠ same residue
DNAJC19 p.Gly68Val Uncertain significance ★ ⚠ 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
DNAJC19 p.Arg20Cys 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-gly68ser (accessed [today's date]).

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