Is DNAJC28 p.Asp329His (c.985G>C) pathogenic?

DNAJC28 p.Asp329His (c.985G>C) is classified Uncertain significance in DNAJC28 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.2255); Very rare (popmax 0.00189%, amr).

How common is DNAJC28 p.Asp329His (c.985G>C) in the general population?

DNAJC28 p.Asp329His (c.985G>C) is very rare (popmax 0.00189%, amr) (gnomAD).

What do computational predictors say about DNAJC28 p.Asp329His (c.985G>C)?

AlphaMissense predicts likely benign (score 0.2255) — an in-silico prediction, not a clinical call.

DNAJC28 p.Asp329His

c.985G>C · rs754237121 · VCV3084572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2255 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00189%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2255	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -7.40	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 0.8	GERP 0.61, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 1,163 bp · p 0.54 · regional, not allelic
Overall
CADD	21.5	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 0.00189% Admixed American · 1/53,042 alleles

Overall 0.000189% 3/1,590,156 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00189%	53,042
Remaining individualsnot grpmax-eligible	0.00163%	61,370
European (non-Finnish)	8.52e-05%	1,173,162

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: DNAJC28
Protein: p.Asp329His
Coding: c.985G>C
MANE Select: NM_001040192
dbSNP: rs754237121
Type: single nucleotide variant
Location: chr21:33488409 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 75.15

Full DNAJC28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC28 p.Arg134Gln Uncertain significance ★ same type
DNAJC28 p.Arg202Cys Uncertain significance ★ same type
DNAJC28 p.Arg202His Uncertain significance ★ same type
DNAJC28 p.Arg310Gln Uncertain significance ★ ⚠ same type
DNAJC28 p.Arg310Gly Uncertain significance ★ ⚠ same type
DNAJC28 p.Asn378Asp Uncertain significance ★ ⚠ same type
DNAJC28 p.Asp352Val Uncertain significance ★ ⚠ same type
DNAJC28 p.Asp88Asn 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/dnajc28-p-asp329his (accessed [today's date]).

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