Is DNAJC13 p.Arg73Cys (c.217C>T) pathogenic?

DNAJC13 p.Arg73Cys (c.217C>T) is classified Uncertain significance in DNAJC13 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-13). AlphaMissense: likely pathogenic (0.7302); Ultra-rare (popmax 0.0407%, amr).

How common is DNAJC13 p.Arg73Cys (c.217C>T) in the general population?

DNAJC13 p.Arg73Cys (c.217C>T) is ultra-rare (popmax 0.0407%, amr) (gnomAD).

What do computational predictors say about DNAJC13 p.Arg73Cys (c.217C>T)?

AlphaMissense predicts likely pathogenic (score 0.7302) — an in-silico prediction, not a clinical call.

DNAJC13 p.Arg73Cys

c.217C>T · rs267599610 · VCV2266376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7302 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0407%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7302	likely pathogenic
REVEL	0.295	indeterminate
SaProt	LLR -9.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 41 kb · p 7.6e-11 · regional, not allelic
Overall
CADD	28.1	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 0.0407% Admixed American · 24/58,954 alleles

Filtering AF 0.028% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0238%

Overall 0.00286% 46/1,607,982 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0407%	2,456
Remaining individualsnot grpmax-eligible	0.00483%	20,719
East Asian	0.00226%	44,332
European (non-Finnish)	0.00153%	65,414

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.Arg73Cys
Coding: c.217C>T
MANE Select: NM_015268
dbSNP: rs267599610
Type: single nucleotide variant
Location: chr3:132447393 (GRCh38)
Gene constraint: LOEUF 0.267 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.91
Residue 73: the 'involved in membrane association' region

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

Similar variants

DNAJC13 p.Arg73Gly Uncertain significance ★ ⚠ same residue
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

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-arg73cys (accessed [today's date]).

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