Is DNAJC6 p.Val295Phe (c.883G>T) pathogenic?

DNAJC6 p.Val295Phe (c.883G>T) is classified Uncertain significance in DNAJC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: likely pathogenic (0.5742); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DNAJC6 p.Val295Phe (c.883G>T)?

DNAJC6 p.Val295Phe (c.883G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJC6 p.Val295Phe (c.883G>T) in the general population?

DNAJC6 p.Val295Phe (c.883G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJC6 p.Val295Phe (c.883G>T)?

AlphaMissense predicts likely pathogenic (score 0.5742) — an in-silico prediction, not a clinical call.

DNAJC6 p.Val295Phe

c.883G>T · VCV4617725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5742 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5742	likely pathogenic
REVEL	0.488	indeterminate
SaProt	LLR -8.01	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 4.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 103 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V238F vs ClinVar V295F) — 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.Val295Phe
Coding: c.883G>T
MANE Select: NM_001256864
Type: single nucleotide variant
Location: chr1:65385794 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.29
Residue 295: the c2 tensin-type domain

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-val295phe (accessed [today's date]).

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