Is DNAJC5 p.Ala140Val (c.419C>T) pathogenic?

DNAJC5 p.Ala140Val (c.419C>T) is classified Conflicting classifications of pathogenicity in DNAJC5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-13). AlphaMissense: likely benign (0.0813); Ultra-rare (popmax 0.029%, eas); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with DNAJC5 p.Ala140Val (c.419C>T)?

DNAJC5 p.Ala140Val (c.419C>T) is associated with neuronal ceroid lipofuscinosis (ClinVar).

How common is DNAJC5 p.Ala140Val (c.419C>T) in the general population?

DNAJC5 p.Ala140Val (c.419C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about DNAJC5 p.Ala140Val (c.419C>T)?

AlphaMissense predicts likely benign (score 0.0813) — an in-silico prediction, not a clinical call.

DNAJC5 p.Ala140Val

c.419C>T · rs144915847 · VCV205374

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0813 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.0813	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -4.38	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 714 bp · p 0.018 · regional, not allelic
Overall
CADD	21.3	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 0.029% East Asian · 13/44,900 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0075% 121/1,614,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,454
Middle Eastern	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0112%	8,926
European (non-Finnish)	0.0078%	12,827
African / African-American	0.00534%	18,737
South Asian	0.00329%	30,365
Admixed American	0.00167%	60,014

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.Ala140Val
Coding: c.419C>T
MANE Select: NM_025219
dbSNP: rs144915847
Type: single nucleotide variant
Location: chr20:63930948 (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.Ala140= 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-ala140val (accessed [today's date]).

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