Is DNAJC13 p.Val1995Ile (c.5983G>A) pathogenic?

DNAJC13 p.Val1995Ile (c.5983G>A) is classified Uncertain significance in DNAJC13 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-05). AlphaMissense: likely benign (0.1918); Ultra-rare (popmax 0.0183%, amr); Associated with DNAJC13-related disorder.

What condition is associated with DNAJC13 p.Val1995Ile (c.5983G>A)?

DNAJC13 p.Val1995Ile (c.5983G>A) is associated with DNAJC13-related disorder (ClinVar).

How common is DNAJC13 p.Val1995Ile (c.5983G>A) in the general population?

DNAJC13 p.Val1995Ile (c.5983G>A) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about DNAJC13 p.Val1995Ile (c.5983G>A)?

AlphaMissense predicts likely benign (score 0.1918) — an in-silico prediction, not a clinical call.

DNAJC13 p.Val1995Ile

c.5983G>A · rs10935014 · VCV3036719

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1918 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DNAJC13-related disorder

Computational evidence

Protein change
AlphaMissense	0.1918	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -1.25	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 9.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 60 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	26.0	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 0.0183% Admixed American · 11/60,020 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.0026% 42/1,614,090 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,456
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.00246%	40,688

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: DNAJC13
Protein: p.Val1995Ile
Coding: c.5983G>A
MANE Select: NM_015268
dbSNP: rs10935014
Type: single nucleotide variant
Location: chr3:132523636 (GRCh38)
Gene constraint: LOEUF 0.267 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.91
Residue 1995: a UniProt-annotated variant site (in)

Full DNAJC13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNAJC13-related disorder

Similar variants

DNAJC13 p.Val1995Leu Benign/Likely benign ★★ ⚠ same residue
DNAJC13 p.Ile2055Leu Uncertain significance ★★ ⚠ same condition
DNAJC13 p.Thr66Met Uncertain significance ★★ ⚠ same condition
DNAJC13 p.His33Arg Uncertain significance ★ ⚠ same condition
DNAJC13 p.Ile1691Val Uncertain significance ★ ⚠ same condition
DNAJC13 p.Ala1839Val Uncertain significance ⚠ same condition
DNAJC13 p.Ala183Val Uncertain significance ⚠ same condition
DNAJC13 p.Cys1083Ser 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/dnajc13-p-val1995ile (accessed [today's date]).

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