Is DNAJC30 p.Pro78Ser (c.232C>T) pathogenic?

DNAJC30 p.Pro78Ser (c.232C>T) is classified Pathogenic in DNAJC30 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely pathogenic (0.9487); Absent from gnomAD v4.1; Associated with Leber-like hereditary optic neuropathy, autosomal recessive 1.

What condition is associated with DNAJC30 p.Pro78Ser (c.232C>T)?

DNAJC30 p.Pro78Ser (c.232C>T) is associated with Leber-like hereditary optic neuropathy, autosomal recessive 1 (ClinVar).

How common is DNAJC30 p.Pro78Ser (c.232C>T) in the general population?

DNAJC30 p.Pro78Ser (c.232C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJC30 p.Pro78Ser (c.232C>T)?

AlphaMissense predicts likely pathogenic (score 0.9487) — an in-silico prediction, not a clinical call.

DNAJC30 p.Pro78Ser

c.232C>T · rs2116654445 · VCV1171026

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9487 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Leber-like hereditary optic neuropathy, autosomal recessive 1

Computational evidence

Protein change
AlphaMissense	0.9487	likely pathogenic ✓ concordant with ClinVar · top 4% in DNAJC30
REVEL	0.882	moderately pathogenic-leaning
SaProt	LLR -14.26	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAJC30
Protein: p.Pro78Ser
Coding: c.232C>T
MANE Select: NM_032317
dbSNP: rs2116654445
Type: single nucleotide variant
Location: chr7:73683192 (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.Pro78Arg Uncertain significance ★ ⚠ 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-pro78ser (accessed [today's date]).

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