Is DNAJC19 p.Arg61Trp (c.181C>T) pathogenic?

DNAJC19 p.Arg61Trp (c.181C>T) is classified Conflicting classifications of pathogenicity in DNAJC19 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-28). AlphaMissense: likely pathogenic (0.8915); Rare (popmax 0.216%, sas); Associated with Inborn genetic diseases.

What condition is associated with DNAJC19 p.Arg61Trp (c.181C>T)?

DNAJC19 p.Arg61Trp (c.181C>T) is associated with Inborn genetic diseases, 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 p.Arg61Trp (c.181C>T) in the general population?

DNAJC19 p.Arg61Trp (c.181C>T) is rare (popmax 0.216%, sas) (gnomAD).

What do computational predictors say about DNAJC19 p.Arg61Trp (c.181C>T)?

AlphaMissense predicts likely pathogenic (score 0.8915) — an in-silico prediction, not a clinical call.

DNAJC19 p.Arg61Trp

c.181C>T · rs141007488 · VCV214298

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8915 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.216%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8915	likely pathogenic
REVEL	0.301	indeterminate
SaProt	LLR -14.79	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	loss · gain 0.12 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 8.7	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 4,959 bp · p 0.0025 · regional, not allelic
Overall
CADD	25.2	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 0.216% South Asian · 197/91,072 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.182%

Overall 0.0151% 244/1,613,866 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.216%	462
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Middle Eastern	0.033%	3,031
Finnishnot grpmax-eligible	0.0141%	7,110
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
Admixed American	0.00333%	30,006
East Asian	0.00223%	44,844
African / African-American	0.00133%	75,008
European (non-Finnish)	0.000593%	168,552

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.Arg61Trp
Coding: c.181C>T
MANE Select: NM_145261
dbSNP: rs141007488
Type: single nucleotide variant
Location: chr3:180986971 (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

Also linked: 3-methylglutaconic aciduria type 5

Similar variants

DNAJC19 p.Arg61Gln Conflicting classifications of pathogenicity ★ ⚠ 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-arg61trp (accessed [today's date]).

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