Is DNAJC6 p.Ala596Ser (c.1786G>T) pathogenic?

DNAJC6 p.Ala596Ser (c.1786G>T) is classified Uncertain significance in DNAJC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.0708); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with DNAJC6 p.Ala596Ser (c.1786G>T)?

DNAJC6 p.Ala596Ser (c.1786G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJC6 p.Ala596Ser (c.1786G>T) in the general population?

DNAJC6 p.Ala596Ser (c.1786G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DNAJC6 p.Ala596Ser (c.1786G>T)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

DNAJC6 p.Ala596Ser

c.1786G>T · VCV4617722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -5.39	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 2	GERP 3.8, phastCons 0.28
Regional constraint	o/e 0.85	unconstrained · MANE · 103 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	12.36	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A539S vs ClinVar A596S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,882 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,612,960 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,441
European (non-Finnish)	0.00017%	589,797

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: DNAJC6
Protein: p.Ala596Ser
Coding: c.1786G>T
MANE Select: NM_001256864
Type: single nucleotide variant
Location: chr1:65392748 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.29
Residue 596: the 'disordered' region

Full DNAJC6 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

Similar variants

DNAJC6 p.Ala226Val Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Ala234Thr Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Ala626Val Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Ala770Val Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Arg174Gln Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Arg335His Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Arg823His Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Asp691Gly 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/dnajc6-p-ala596ser (accessed [today's date]).

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