Is DNAJC28 p.Ser89Cys (c.266C>G) pathogenic?

DNAJC28 p.Ser89Cys (c.266C>G) is classified Uncertain significance in DNAJC28 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.1133); Ultra-rare (popmax 0.0668%, eas).

How common is DNAJC28 p.Ser89Cys (c.266C>G) in the general population?

DNAJC28 p.Ser89Cys (c.266C>G) is ultra-rare (popmax 0.0668%, eas) (gnomAD).

What do computational predictors say about DNAJC28 p.Ser89Cys (c.266C>G)?

AlphaMissense predicts likely benign (score 0.1133) — an in-silico prediction, not a clinical call.

DNAJC28 p.Ser89Cys

c.266C>G · rs767409884 · VCV3084570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1133 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0668%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1133	likely benign
REVEL	0.414	indeterminate
SaProt	LLR -10.30	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 5.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 1,163 bp · p 0.54 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0668% East Asian · 30/44,884 alleles

Filtering AF 0.0481% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0417%

Overall 0.00273% 44/1,613,752 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0668%	1,496
Remaining individualsnot grpmax-eligible	0.0176%	5,680
Admixed American	0.005%	19,981

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.Ser89Cys
Coding: c.266C>G
MANE Select: NM_001040192
dbSNP: rs767409884
Type: single nucleotide variant
Location: chr21:33489128 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 75.15
Residue 89: the j domain

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.Asp329His Uncertain significance ★ ⚠ same type
DNAJC28 p.Asp352Val 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-ser89cys (accessed [today's date]).

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