Is DNAJC17 p.Arg157Ser (c.471G>T) pathogenic?

DNAJC17 p.Arg157Ser (c.471G>T) is classified Uncertain significance in DNAJC17 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-03). AlphaMissense: likely benign (0.1986); Ultra-rare (popmax 0.012%, afr).

How common is DNAJC17 p.Arg157Ser (c.471G>T) in the general population?

DNAJC17 p.Arg157Ser (c.471G>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about DNAJC17 p.Arg157Ser (c.471G>T)?

AlphaMissense predicts likely benign (score 0.1986) — an in-silico prediction, not a clinical call.

DNAJC17 p.Arg157Ser

c.471G>T · rs779888515 · VCV1898649

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1986 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1986	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.34	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.006	GERP -0.72, phastCons 0.031
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.95 · regional, not allelic
Overall
CADD	17.17	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 0.012% African / African-American · 9/74,918 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.000558% 9/1,613,564 alleles · ultra-rare

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.Arg157Ser
Coding: c.471G>T
MANE Select: NM_018163
dbSNP: rs779888515
Type: single nucleotide variant
Location: chr15:40776203 (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.Arg157Thr 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-arg157ser (accessed [today's date]).

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