Is DNAJC5 p.Ser188Phe (c.563C>T) pathogenic?

DNAJC5 p.Ser188Phe (c.563C>T) is classified Uncertain significance in DNAJC5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-07-15). AlphaMissense: ambiguous (0.3881); Very rare (popmax 8.56e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAJC5 p.Ser188Phe (c.563C>T)?

DNAJC5 p.Ser188Phe (c.563C>T) is associated with Inborn genetic diseases, ceroid lipofuscinosis, neuronal, 4 (Kufs type), neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Ser188Phe (c.563C>T) in the general population?

DNAJC5 p.Ser188Phe (c.563C>T) is very rare (popmax 8.56e-05%, nfe) (gnomAD).

What do computational predictors say about DNAJC5 p.Ser188Phe (c.563C>T)?

AlphaMissense predicts ambiguous (score 0.3881) — an in-silico prediction, not a clinical call.

DNAJC5 p.Ser188Phe

c.563C>T · rs753155376 · VCV2159688

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3881 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.56e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3881	ambiguous
REVEL	0.188	benign-leaning
SaProt	LLR -10.40	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 714 bp · p 0.018 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 8.56e-05% European (non-Finnish) · 1/1,168,794 alleles

Overall 0.000657% 1/152,100 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.Ser188Phe
Coding: c.563C>T
MANE Select: NM_025219
dbSNP: rs753155376
Type: single nucleotide variant
Location: chr20:63931534 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ceroid lipofuscinosis, neuronal, 4 (Kufs type)neuronal ceroid lipofuscinosis

Similar variants

DNAJC5 p.Leu115Arg Pathogenic ★★ same condition
DNAJC5 c.-109A>G Uncertain significance ★★ same condition
DNAJC5 c.-11-2A>G Uncertain significance ★★ same condition
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

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-ser188phe (accessed [today's date]).

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