Is DNAJC19 p.Ala63Val (c.188C>T) pathogenic?

DNAJC19 p.Ala63Val (c.188C>T) is classified Uncertain significance in DNAJC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely pathogenic (0.9946); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAJC19 p.Ala63Val (c.188C>T)?

DNAJC19 p.Ala63Val (c.188C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJC19 p.Ala63Val (c.188C>T) in the general population?

DNAJC19 p.Ala63Val (c.188C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about DNAJC19 p.Ala63Val (c.188C>T)?

AlphaMissense predicts likely pathogenic (score 0.9946) — an in-silico prediction, not a clinical call.

DNAJC19 p.Ala63Val

c.188C>T · rs1435505055 · VCV3084527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9946 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9946	likely pathogenic
REVEL	0.865	moderately pathogenic-leaning
SaProt	LLR -14.46	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.48	donor loss, 21 bp away · masked 0 · deltas
Pangolin	Δ0.38	loss · gain 0.24 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 10	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 4,959 bp · p 0.0025 · regional, not allelic
Overall
CADD	33.0	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 0.000339% European (non-Finnish) · 4/1,179,854 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,736 alleles · very rare exomes 3/1,461,608 · genomes 1/152,128 · joint denominator

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.Ala63Val
Coding: c.188C>T
MANE Select: NM_145261
dbSNP: rs1435505055
Type: single nucleotide variant
Location: chr3:180986964 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50
Residue 63: 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

Similar variants

DNAJC19 p.Ala25Thr Uncertain significance ★★ ⚠ same condition
DNAJC19 p.Arg20Cys 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
DNAJC19 p.Arg61Gln Conflicting classifications of pathogenicity ★ ⚠ 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-ala63val (accessed [today's date]).

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