Is DNAJC12 p.Pro47His (c.140C>A) pathogenic?

DNAJC12 p.Pro47His (c.140C>A) is classified Uncertain significance in DNAJC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). AlphaMissense: likely benign (0.2953); Very rare (popmax 0.0011%, sas).

How common is DNAJC12 p.Pro47His (c.140C>A) in the general population?

DNAJC12 p.Pro47His (c.140C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DNAJC12 p.Pro47His (c.140C>A)?

AlphaMissense predicts likely benign (score 0.2953) — an in-silico prediction, not a clinical call.

DNAJC12 p.Pro47His

c.140C>A · rs781264201 · VCV2005477

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2953	likely benign
REVEL	0.349	indeterminate
SaProt	LLR -11.45	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 9.6	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 41 kb · p 0.52 · regional, not allelic
Overall
CADD	25.3	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 0.0011% South Asian · 1/91,070 alleles

Overall 6.84e-05% 1/1,461,840 alleles · very rare

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.Pro47His
Coding: c.140C>A
MANE Select: NM_021800
dbSNP: rs781264201
Type: single nucleotide variant
Location: chr10:67823331 (GRCh38)
Gene constraint: LOEUF 1.193 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.84 · 1 PDB
Residue 47: the j domain

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

Similar variants

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
DNAJC12 p.Arg180His 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-pro47his (accessed [today's date]).

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