Is DNAJC5 p.Phe112Leu (c.334T>C) pathogenic?

DNAJC5 p.Phe112Leu (c.334T>C) is classified Uncertain significance in DNAJC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: likely benign (0.2731); Very rare (popmax 8.47e-05%, nfe); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with DNAJC5 p.Phe112Leu (c.334T>C)?

DNAJC5 p.Phe112Leu (c.334T>C) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Phe112Leu (c.334T>C) in the general population?

DNAJC5 p.Phe112Leu (c.334T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DNAJC5 p.Phe112Leu (c.334T>C)?

AlphaMissense predicts likely benign (score 0.2731) — an in-silico prediction, not a clinical call.

DNAJC5 p.Phe112Leu

c.334T>C · rs2516801514 · VCV2005528

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2731 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.2731	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -6.23	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 0.17	GERP -4.3, phastCons 0.012
Regional constraint	o/e 0.79	unconstrained · MANE · 714 bp · p 0.018 · regional, not allelic
Overall
CADD	8.837	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 8.47e-05% European (non-Finnish) · 1/1,179,952 alleles

Overall 6.85e-05% 1/1,460,740 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: DNAJC5
Protein: p.Phe112Leu
Coding: c.334T>C
MANE Select: NM_025219
dbSNP: rs2516801514
Type: single nucleotide variant
Location: chr20:63930863 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB

Full DNAJC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAJC5 p.Phe112= Likely benign ★ same residue
DNAJC5 p.Ala176Val Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Ala26Thr Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Ala54Thr Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Ala54Val Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Ala63Thr Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Arg164Lys Uncertain significance ★★ ⚠ same condition
DNAJC5 p.Arg36Gln Uncertain significance ★★ ⚠ 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/dnajc5-p-phe112leu (accessed [today's date]).

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