Is DNAJC30 p.Ser44fs (c.130_131del) pathogenic?

DNAJC30 p.Ser44fs (c.130131del) is classified Pathogenic in DNAJC30 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-09). Very rare (popmax 0.00167%, amr); Associated with Leber-like hereditary optic neuropathy, autosomal recessive 1.

What condition is associated with DNAJC30 p.Ser44fs (c.130_131del)?

DNAJC30 p.Ser44fs (c.130_131del) is associated with Leber-like hereditary optic neuropathy, autosomal recessive 1 (ClinVar).

How common is DNAJC30 p.Ser44fs (c.130_131del) in the general population?

DNAJC30 p.Ser44fs (c.130_131del) is very rare (popmax 0.00167%, amr) (gnomAD).

DNAJC30 p.Ser44fs

c.130_131del · rs782463803 · VCV2628014

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Leber-like hereditary optic neuropathy, autosomal recessive 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.9	GERP -11
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,016 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000434% 7/1,613,884 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Admixed Americangrpmax	0.00167%	60,016
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000339%	295,014

Ashkenazi Jewish 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: DNAJC30
Protein: p.Ser44fs
Coding: c.130_131del
MANE Select: NM_032317
dbSNP: rs782463803
Type: Deletion
Location: chr7:73683293 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.87 · 1 PDB

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.Tyr51Cys Pathogenic/Likely pathogenic ★★ same condition
DNAJC30 c.*122C>T Uncertain significance ★ same condition
DNAJC30 p.Pro78Arg Uncertain significance ★ ⚠ same condition
DNAJC30 p.Glu204Ter Pathogenic same condition
DNAJC30 p.His77del Pathogenic same condition
DNAJC30 p.Leu101Gln Pathogenic same condition
DNAJC30 p.Pro78Ser Pathogenic same condition

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-ser44fs (accessed [today's date]).

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