Is DNAJC17 p.Arg103Trp (c.307C>T) pathogenic?

DNAJC17 p.Arg103Trp (c.307C>T) is classified Uncertain significance in DNAJC17 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-18). AlphaMissense: likely pathogenic (0.6867); Ultra-rare (popmax 0.0165%, mid).

How common is DNAJC17 p.Arg103Trp (c.307C>T) in the general population?

DNAJC17 p.Arg103Trp (c.307C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DNAJC17 p.Arg103Trp (c.307C>T)?

AlphaMissense predicts likely pathogenic (score 0.6867) — an in-silico prediction, not a clinical call.

DNAJC17 p.Arg103Trp

c.307C>T · VCV3694802

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6867 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6867	likely pathogenic
REVEL	0.372	indeterminate
SaProt	LLR -14.28	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 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.95 · regional, not allelic
Overall
CADD	27.6	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00157% 23/1,461,652 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.00186%	53,636

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.Arg103Trp
Coding: c.307C>T
MANE Select: NM_018163
Type: single nucleotide variant
Location: chr15:40776616 (GRCh38)
Gene constraint: LOEUF 0.95 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.72 · 1 PDB
Residue 103: the 'disordered' region

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

Similar variants

DNAJC17 p.Arg103Gln 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.Arg105Trp Uncertain significance ★★ ⚠ same type
DNAJC17 p.Arg119Trp Uncertain significance ★★ ⚠ same type
DNAJC17 p.Arg151Cys Uncertain significance ★★ ⚠ same type
DNAJC17 p.Arg151Leu 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-arg103trp (accessed [today's date]).

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