Is DNAJC30 p.Pro78Arg (c.233C>G) pathogenic?

DNAJC30 p.Pro78Arg (c.233C>G) is classified Uncertain significance in DNAJC30 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: likely pathogenic (0.8478); Very rare (popmax 0.0011%, sas); Associated with Leber-like hereditary optic neuropathy, autosomal recessive 1.

What condition is associated with DNAJC30 p.Pro78Arg (c.233C>G)?

DNAJC30 p.Pro78Arg (c.233C>G) is associated with Leber-like hereditary optic neuropathy, autosomal recessive 1 (ClinVar).

How common is DNAJC30 p.Pro78Arg (c.233C>G) in the general population?

DNAJC30 p.Pro78Arg (c.233C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DNAJC30 p.Pro78Arg (c.233C>G)?

AlphaMissense predicts likely pathogenic (score 0.8478) — an in-silico prediction, not a clinical call.

DNAJC30 p.Pro78Arg

c.233C>G · rs782695672 · VCV3251975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8478 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Leber-like hereditary optic neuropathy, autosomal recessive 1

Computational evidence

Protein change
AlphaMissense	0.8478	likely pathogenic
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -16.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 7.2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 677 bp · p 0.083 · regional, not allelic
Overall
CADD	33.0	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 0.0011% South Asian · 1/91,090 alleles

Overall 6.84e-05% 1/1,461,808 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: DNAJC30
Protein: p.Pro78Arg
Coding: c.233C>G
MANE Select: NM_032317
dbSNP: rs782695672
Type: single nucleotide variant
Location: chr7:73683191 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.87 · 1 PDB
Residue 78: a turn; the j domain; a UniProt-annotated variant site (in lhonar1; results in reduced turnover of n-module subunits of the respiratory chain complex i and reduced complex i activity in homozygous patient-derived cells)

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

Disease context

Leber-like hereditary optic neuropathy, autosomal recessive 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAJC30 p.Pro78Ser Pathogenic same residue
DNAJC30 p.Tyr51Cys Pathogenic/Likely pathogenic ★★ same condition
DNAJC30 c.*122C>T Uncertain significance ★ same condition
DNAJC30 p.Glu204Ter Pathogenic same condition
DNAJC30 p.Leu101Gln Pathogenic same condition
DNAJC30 p.His77del Pathogenic same condition
DNAJC30 p.Ser44fs Pathogenic same condition
DNAJC30 p.Gly34Arg Benign ★★ 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-pro78arg (accessed [today's date]).

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