Is DNAJC30 p.Pro133Ser (c.397C>T) pathogenic?

DNAJC30 p.Pro133Ser (c.397C>T) is classified Uncertain significance in DNAJC30 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.0635); Ultra-rare (popmax 0.02%, nfe).

How common is DNAJC30 p.Pro133Ser (c.397C>T) in the general population?

DNAJC30 p.Pro133Ser (c.397C>T) is ultra-rare (popmax 0.02%, nfe) (gnomAD).

What do computational predictors say about DNAJC30 p.Pro133Ser (c.397C>T)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

DNAJC30 p.Pro133Ser

c.397C>T · rs782179907 · VCV2657565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.57	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 0.57	GERP -0.13
Regional constraint	o/e 1.10	unconstrained · MANE · 677 bp · p 0.083 · regional, not allelic
Overall
CADD	7.432	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 0.02% European (non-Finnish) · 233/1,165,754 alleles

Filtering AF 0.0179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.017%

Overall 0.0149% 237/1,588,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.02%	5,003
Remaining individualsnot grpmax-eligible	0.00326%	30,631
African / African-American	0.00135%	74,316
South Asian	0.00113%	88,348

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: DNAJC30
Protein: p.Pro133Ser
Coding: c.397C>T
MANE Select: NM_032317
dbSNP: rs782179907
Type: single nucleotide variant
Location: chr7:73683027 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.87 · 1 PDB
Residue 133: the 'disordered' region

Full DNAJC30 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC30 p.Pro133Leu Uncertain significance ★ ⚠ same residue
DNAJC30 p.Tyr51Cys Pathogenic/Likely pathogenic ★★ same type
DNAJC30 p.Gly34Arg Benign ★★ same type
DNAJC30 p.Trp8Ter Likely pathogenic ★ same type
DNAJC30 p.Tyr98Ser Likely pathogenic ★ same type
DNAJC30 c.*122C>T Uncertain significance ★ same type
DNAJC30 p.Ala153Ser Uncertain significance ★ ⚠ same type
DNAJC30 p.Ala157Val 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/dnajc30-p-pro133ser (accessed [today's date]).

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