Is DNAJC5 p.Tyr76= (c.228C>T) pathogenic?

DNAJC5 p.Tyr76= (c.228C>T) is classified Benign/Likely benign in DNAJC5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Rare (popmax 0.173%, amr); Associated with Inborn genetic diseases.

What condition is associated with DNAJC5 p.Tyr76= (c.228C>T)?

DNAJC5 p.Tyr76= (c.228C>T) is associated with Inborn genetic diseases, neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Tyr76= (c.228C>T) in the general population?

DNAJC5 p.Tyr76= (c.228C>T) is rare (popmax 0.173%, amr) (gnomAD).

DNAJC5 p.Tyr76=

c.228C>T · rs201495666 · VCV241601

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.173%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.41	GERP -1.2, phastCons 0.11
Overall
CADD	12.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.173% Admixed American · 104/60,024 alleles

Filtering AF 0.146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.0182% 294/1,614,222 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.173%	577
Remaining individualsnot grpmax-eligible	0.0336%	2,977
African / African-American	0.032%	3,128
East Asian	0.0267%	3,739
European (non-Finnish)	0.0112%	8,940
Finnishnot grpmax-eligible	0.00156%	64,024

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.Tyr76=
Coding: c.228C>T
MANE Select: NM_025219
dbSNP: rs201495666
Type: single nucleotide variant
Location: chr20:63929432 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.09 · 2 PDB
Residue 76: the j domain; an α-helix

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: neuronal ceroid lipofuscinosis

Similar variants

DNAJC5 p.Tyr76His Uncertain significance ★ ⚠ 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-tyr76 (accessed [today's date]).

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