Is DNAJC17 p.Arg130Cys (c.388C>T) pathogenic?

DNAJC17 p.Arg130Cys (c.388C>T) is classified Uncertain significance in DNAJC17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-25). AlphaMissense: ambiguous (0.5156); Ultra-rare (popmax 0.012%, afr).

How common is DNAJC17 p.Arg130Cys (c.388C>T) in the general population?

DNAJC17 p.Arg130Cys (c.388C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about DNAJC17 p.Arg130Cys (c.388C>T)?

AlphaMissense predicts ambiguous (score 0.5156) — an in-silico prediction, not a clinical call.

DNAJC17 p.Arg130Cys

c.388C>T · rs534789773 · VCV1448582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5156 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Computational evidence

Protein change
AlphaMissense	0.5156	ambiguous
REVEL	0.593	indeterminate
SaProt	LLR -11.40	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.52, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.95 · regional, not allelic
Overall
CADD	33.0	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 0.012% African / African-American · 9/75,028 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00211% 34/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,336
South Asian	0.00659%	15,174
Remaining individualsnot grpmax-eligible	0.0032%	31,254
Admixed American	0.00167%	60,002
Finnishnot grpmax-eligible	0.00156%	63,992
European (non-Finnish)	0.00127%	78,665

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: DNAJC17
Protein: p.Arg130Cys
Coding: c.388C>T
MANE Select: NM_018163
dbSNP: rs534789773
Type: single nucleotide variant
Location: chr15:40776286 (GRCh38)
Gene constraint: LOEUF 0.95 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.72 · 1 PDB
Residue 130: the 'disordered' region

Full DNAJC17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC17 p.Arg130His Uncertain significance ★ ⚠ same residue
DNAJC17 p.Ala227= Uncertain significance ★★ same type
DNAJC17 p.Ala23Glu Uncertain significance ★★ ⚠ same type
DNAJC17 p.Ala35Thr Uncertain significance ★★ ⚠ same type
DNAJC17 p.Arg103Trp Uncertain significance ★★ ⚠ same type
DNAJC17 p.Arg105Trp Uncertain significance ★★ ⚠ same type
DNAJC17 p.Arg119Trp Uncertain significance ★★ ⚠ same type
DNAJC17 p.Arg151Cys Uncertain significance ★★ ⚠ 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/dnajc17-p-arg130cys (accessed [today's date]).

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