Is DNAJC4 p.Arg92His (c.275G>A) pathogenic?

DNAJC4 p.Arg92His (c.275G>A) is classified Uncertain significance in DNAJC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely pathogenic (0.678); Very rare (popmax 0.00446%, eas).

How common is DNAJC4 p.Arg92His (c.275G>A) in the general population?

DNAJC4 p.Arg92His (c.275G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DNAJC4 p.Arg92His (c.275G>A)?

AlphaMissense predicts likely pathogenic (score 0.678) — an in-silico prediction, not a clinical call.

DNAJC4 p.Arg92His

c.275G>A · rs769533900 · VCV3084583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.678 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.678	likely pathogenic
REVEL	0.793	moderately pathogenic-leaning
SaProt	LLR -12.82	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,326 bp · p 0.24 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00217% 35/1,613,182 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,440
European (non-Finnish)	0.00271%	36,860
Admixed American	0.00167%	59,934

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: DNAJC4
Protein: p.Arg92His
Coding: c.275G>A
MANE Select: NM_005528
dbSNP: rs769533900
Type: single nucleotide variant
Location: chr11:64232524 (GRCh38)
Gene constraint: LOEUF 1.444 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.83
Residue 92: the j domain; the 'disordered' region

Full DNAJC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC4 p.Arg92Cys Uncertain significance ★ ⚠ same residue
DNAJC4 p.Ala200Asp Uncertain significance ★ ⚠ same type
DNAJC4 p.Ala204Pro Uncertain significance ★ ⚠ same type
DNAJC4 p.Ala26Thr Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg100Cys Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg100His Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg109Pro Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg15Gly 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/dnajc4-p-arg92his (accessed [today's date]).

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