Is DNAJC13 p.Arg1997Ile (c.5990G>T) pathogenic?

DNAJC13 p.Arg1997Ile (c.5990G>T) is classified Uncertain significance in DNAJC13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely pathogenic (0.9959); Very rare (popmax 0.00534%, afr).

How common is DNAJC13 p.Arg1997Ile (c.5990G>T) in the general population?

DNAJC13 p.Arg1997Ile (c.5990G>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about DNAJC13 p.Arg1997Ile (c.5990G>T)?

AlphaMissense predicts likely pathogenic (score 0.9959) — an in-silico prediction, not a clinical call.

DNAJC13 p.Arg1997Ile

c.5990G>T · VCV4661348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9959	likely pathogenic · top 4% in DNAJC13
REVEL	0.592	indeterminate
SaProt	LLR -10.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 60 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	29.6	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 0.00534% African / African-American · 4/74,926 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00031% 5/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,732
Admixed American	0.00167%	60,000

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.Arg1997Ile
Coding: c.5990G>T
MANE Select: NM_015268
Type: single nucleotide variant
Location: chr3:132523643 (GRCh38)
Gene constraint: LOEUF 0.267 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.91

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

Similar variants

DNAJC13 p.Arg677Trp Uncertain significance ★★ ⚠ same type
DNAJC13 p.Arg833Lys Uncertain significance ★★ ⚠ same type
DNAJC13 p.Ile2055Leu Uncertain significance ★★ ⚠ same type
DNAJC13 p.Leu1834Val Uncertain significance ★★ ⚠ same type
DNAJC13 p.Met688Val Uncertain significance ★★ ⚠ same type
DNAJC13 p.Thr66Met Uncertain significance ★★ ⚠ same type
DNAJC13 c.1349+102C>T Benign ★★ same type
DNAJC13 c.1349+103C>A Benign ★★ same type

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-arg1997ile (accessed [today's date]).

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