Is DNAJC19 p.Ile99Val (c.295A>G) pathogenic?

DNAJC19 p.Ile99Val (c.295A>G) is classified Uncertain significance in DNAJC19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-14). AlphaMissense: likely benign (0.1048); Very rare (popmax 0.0067%, amr); Associated with Inborn genetic diseases.

What condition is associated with DNAJC19 p.Ile99Val (c.295A>G)?

DNAJC19 p.Ile99Val (c.295A>G) is associated with Inborn genetic diseases, 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 p.Ile99Val (c.295A>G) in the general population?

DNAJC19 p.Ile99Val (c.295A>G) is very rare (popmax 0.0067%, amr) (gnomAD).

What do computational predictors say about DNAJC19 p.Ile99Val (c.295A>G)?

AlphaMissense predicts likely benign (score 0.1048) — an in-silico prediction, not a clinical call.

DNAJC19 p.Ile99Val

c.295A>G · rs762783413 · VCV1002196

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1048 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1048	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -7.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -1.2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 4,959 bp · p 0.0025 · regional, not allelic
Overall
CADD	18.35	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

Grpmax group 0.0067% Admixed American · 4/59,666 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000933% 15/1,607,270 alleles · very rare exomes 13/1,455,100 · genomes 2/152,170 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0067%	14,916
African / African-American	0.00134%	74,756
European (non-Finnish)	0.000851%	117,540

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.Ile99Val
Coding: c.295A>G
MANE Select: NM_145261
dbSNP: rs762783413
Type: single nucleotide variant
Location: chr3:180984696 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50
Residue 99: 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.Ile99fs 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
DNAJC19 p.Arg84Gln 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-ile99val (accessed [today's date]).

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