Is DNAJC8 p.Gly8Arg (c.22G>C) pathogenic?

DNAJC8 p.Gly8Arg (c.22G>C) is classified Uncertain significance in DNAJC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely benign (0.3209); Very rare (popmax 0.0011%, sas).

How common is DNAJC8 p.Gly8Arg (c.22G>C) in the general population?

DNAJC8 p.Gly8Arg (c.22G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DNAJC8 p.Gly8Arg (c.22G>C)?

AlphaMissense predicts likely benign (score 0.3209) — an in-silico prediction, not a clinical call.

DNAJC8 p.Gly8Arg

c.22G>C · rs2524288991 · VCV3084608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3209 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3209	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -8.30	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 3.9	GERP 1.2, phastCons 1
Regional constraint	o/e 1.50	unconstrained · MANE · 73 bp · p 0.0044 · regional, not allelic
Overall
CADD	22.6	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 0.0011% South Asian · 1/91,080 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,460,684 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,080
European (non-Finnish)	0.000339%	295,003

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: DNAJC8
Protein: p.Gly8Arg
Coding: c.22G>C
MANE Select: NM_014280
dbSNP: rs2524288991
Type: single nucleotide variant
Location: chr1:28232977 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.60 · 1 PDB

Full DNAJC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC8 p.Ala161Thr Uncertain significance ★ ⚠ same type
DNAJC8 p.Ala93Val Uncertain significance ★ ⚠ same type
DNAJC8 p.Arg95Gly Uncertain significance ★ ⚠ same type
DNAJC8 p.Asn55Ser Uncertain significance ★ ⚠ same type
DNAJC8 p.Asp92Val Uncertain significance ★ ⚠ same type
DNAJC8 p.Glu179Asp Uncertain significance ★ ⚠ same type
DNAJC8 p.Glu67Lys Uncertain significance ★ ⚠ same type
DNAJC8 p.Gly11Asp 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/dnajc8-p-gly8arg (accessed [today's date]).

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