Is DNAJC12 p.Ser84= (c.252G>A) pathogenic?

DNAJC12 p.Ser84= (c.252G>A) is classified Likely benign in DNAJC12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-18). Very rare (popmax 0.01%, nfe).

How common is DNAJC12 p.Ser84= (c.252G>A) in the general population?

DNAJC12 p.Ser84= (c.252G>A) is very rare (popmax 0.01%, nfe) (gnomAD).

DNAJC12 p.Ser84=

c.252G>A · rs202186686 · VCV1560396

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.01%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.3
Overall
CADD	1.341	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% European (non-Finnish) · 118/1,180,038 alleles

Filtering AF 0.00851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00795%

Overall 0.00843% 136/1,614,080 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0112%	8,927
European (non-Finnish)grpmax	0.01%	10,000
Admixed American	0.005%	20,003
East Asian	0.00446%	22,445
African / African-American	0.004%	24,977
South Asian	0.00329%	30,363

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DNAJC12
Protein: p.Ser84=
Coding: c.252G>A
MANE Select: NM_021800
dbSNP: rs202186686
Type: single nucleotide variant
Location: chr10:67811569 (GRCh38)
Gene constraint: LOEUF 1.193 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.84 · 1 PDB
Residue 84: a UniProt-annotated variant site (in hpanbh4; likely pathogenic)

Full DNAJC12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC12 p.Ser84Trp Uncertain significance ★★ ⚠ same residue
DNAJC12 p.Arg72Ter Pathogenic/Likely pathogenic ★★ same type
DNAJC12 p.Gln162Ter Pathogenic/Likely pathogenic ★★ same type
DNAJC12 p.Trp175Ter Pathogenic ★★ same type
DNAJC12 p.Ala144Ser Uncertain significance ★★ ⚠ same type
DNAJC12 p.Ala73Gly Uncertain significance ★★ ⚠ same type
DNAJC12 p.Ala73Val Uncertain significance ★★ ⚠ same type
DNAJC12 p.Arg180Cys 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/dnajc12-p-ser84 (accessed [today's date]).

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