Is DNAJC6 p.Asp161Ala (c.482A>C) pathogenic?

DNAJC6 p.Asp161Ala (c.482A>C) is classified Uncertain significance in DNAJC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely pathogenic (0.6934); Absent from gnomAD v4.1.

How common is DNAJC6 p.Asp161Ala (c.482A>C) in the general population?

DNAJC6 p.Asp161Ala (c.482A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJC6 p.Asp161Ala (c.482A>C)?

AlphaMissense predicts likely pathogenic (score 0.6934) — an in-silico prediction, not a clinical call.

DNAJC6 p.Asp161Ala

c.482A>C · VCV4085841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6934 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6934	likely pathogenic
REVEL	0.62	indeterminate
SaProt	LLR -10.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 6.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 103 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 D104A vs ClinVar D161A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAJC6
Protein: p.Asp161Ala
Coding: c.482A>C
MANE Select: NM_001256864
Type: single nucleotide variant
Location: chr1:65366135 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.29
Residue 161: the phosphatase tensin-type domain

Full DNAJC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC6 p.Arg330Ter Pathogenic ★★ same type
DNAJC6 p.Ala226Val Uncertain significance ★★ ⚠ same type
DNAJC6 p.Ala234Thr Uncertain significance ★★ ⚠ same type
DNAJC6 p.Ala277Thr Uncertain significance ★★ ⚠ same type
DNAJC6 p.Ala611Val Uncertain significance ★★ ⚠ same type
DNAJC6 p.Ala626Val Uncertain significance ★★ ⚠ same type
DNAJC6 p.Ala770Val Uncertain significance ★★ ⚠ same type
DNAJC6 p.Ala836Ser Uncertain significance ★★ ⚠ same type

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-asp161ala (accessed [today's date]).

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