Is DNAJC16 p.Arg486His (c.1457G>A) pathogenic?

DNAJC16 p.Arg486His (c.1457G>A) is classified Uncertain significance in DNAJC16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). AlphaMissense: likely benign (0.1039); Rare (popmax 0.124%, afr).

How common is DNAJC16 p.Arg486His (c.1457G>A) in the general population?

DNAJC16 p.Arg486His (c.1457G>A) is rare (popmax 0.124%, afr) (gnomAD).

What do computational predictors say about DNAJC16 p.Arg486His (c.1457G>A)?

AlphaMissense predicts likely benign (score 0.1039) — an in-silico prediction, not a clinical call.

DNAJC16 p.Arg486His

c.1457G>A · VCV3841528

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1039 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.124%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1039	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -7.26	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 9.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 39 kb · p 0.017 · regional, not allelic
Overall
CADD	28.2	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 0.124% African / African-American · 93/75,048 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.096%

Overall 0.0083% 134/1,613,722 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.124%	807
Remaining individualsnot grpmax-eligible	0.0128%	7,812
East Asian	0.00891%	11,219
Admixed American	0.005%	20,005
South Asian	0.0022%	45,544
European (non-Finnish)	0.00203%	49,151

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: DNAJC16
Protein: p.Arg486His
Coding: c.1457G>A
MANE Select: NM_015291
Type: single nucleotide variant
Location: chr1:15564047 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.54

Full DNAJC16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC16 p.Ala337Gly Uncertain significance ★ ⚠ same type
DNAJC16 p.Ala53Ser Uncertain significance ★ ⚠ same type
DNAJC16 p.Ala53Thr Uncertain significance ★ ⚠ same type
DNAJC16 p.Ala95Thr Uncertain significance ★ ⚠ same type
DNAJC16 p.Arg111His Uncertain significance ★ ⚠ same type
DNAJC16 p.Arg113His Uncertain significance ★ ⚠ same type
DNAJC16 p.Arg134Gln Uncertain significance ★ ⚠ same type
DNAJC16 p.Arg204Lys 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/dnajc16-p-arg486his (accessed [today's date]).

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