Is DNAJC17 p.Arg271Lys (c.812G>A) pathogenic?

DNAJC17 p.Arg271Lys (c.812G>A) is classified Uncertain significance in DNAJC17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.1698); Very rare (popmax 0.00369%, amr).

How common is DNAJC17 p.Arg271Lys (c.812G>A) in the general population?

DNAJC17 p.Arg271Lys (c.812G>A) is very rare (popmax 0.00369%, amr) (gnomAD).

What do computational predictors say about DNAJC17 p.Arg271Lys (c.812G>A)?

AlphaMissense predicts likely benign (score 0.1698) — an in-silico prediction, not a clinical call.

DNAJC17 p.Arg271Lys

c.812G>A · VCV3685334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1698 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00369%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1698	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -5.89	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 6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.30	unconstrained · MANE · 5,809 bp · p 0.014 · regional, not allelic
Overall
CADD	21.3	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 0.00369% Admixed American · 2/54,224 alleles

Filtering AF 0.000612% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000229%

Overall 0.000419% 6/1,431,286 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00369%	27,112
European (non-Finnish)	0.000343%	291,826

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.Arg271Lys
Coding: c.812G>A
MANE Select: NM_018163
Type: single nucleotide variant
Location: chr15:40768043 (GRCh38)
Gene constraint: LOEUF 0.95 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.72 · 1 PDB

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

Similar variants

DNAJC17 p.Arg271Gly Uncertain significance ★ ⚠ same residue
DNAJC17 p.Arg271fs 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

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-arg271lys (accessed [today's date]).

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