Is DNAJC19 p.Arg20Cys (c.58C>T) pathogenic?

DNAJC19 p.Arg20Cys (c.58C>T) is classified Uncertain significance in DNAJC19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-16). AlphaMissense: likely pathogenic (0.8603); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with DNAJC19 p.Arg20Cys (c.58C>T)?

DNAJC19 p.Arg20Cys (c.58C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJC19 p.Arg20Cys (c.58C>T) in the general population?

DNAJC19 p.Arg20Cys (c.58C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DNAJC19 p.Arg20Cys (c.58C>T)?

AlphaMissense predicts likely pathogenic (score 0.8603) — an in-silico prediction, not a clinical call.

DNAJC19 p.Arg20Cys

c.58C>T · rs750384728 · VCV3084530

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8603 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8603	likely pathogenic
REVEL	0.488	indeterminate
SaProt	LLR -14.08	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 4,959 bp · p 0.0025 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00133% African / African-American · 1/75,002 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,886 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,002
European (non-Finnish)	0.000593%	168,574

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.Arg20Cys
Coding: c.58C>T
MANE Select: NM_145261
dbSNP: rs750384728
Type: single nucleotide variant
Location: chr3:180988094 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50

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

Similar variants

DNAJC19 p.Arg20His Conflicting classifications of pathogenicity ★ same residue
DNAJC19 p.Arg20_Tyr21insTer Pathogenic/Likely pathogenic ★★ same residue
DNAJC19 p.Ala25Thr Uncertain significance ★★ ⚠ same condition
DNAJC19 p.Arg84Gln Uncertain significance ★★ ⚠ same condition
DNAJC19 p.Gly68Ser Uncertain significance ★★ ⚠ same condition
DNAJC19 p.Ile66Met Uncertain significance ★★ ⚠ same condition
DNAJC19 p.Ile99Val Uncertain significance ★★ ⚠ same condition
DNAJC19 p.Val22Ile 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-arg20cys (accessed [today's date]).

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