Is DNAJC6 p.Thr899Ser (c.2696C>G) pathogenic?

DNAJC6 p.Thr899Ser (c.2696C>G) is classified Uncertain significance in DNAJC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-29). AlphaMissense: likely benign (0.2189); Absent from gnomAD v4.1.

How common is DNAJC6 p.Thr899Ser (c.2696C>G) in the general population?

DNAJC6 p.Thr899Ser (c.2696C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJC6 p.Thr899Ser (c.2696C>G)?

AlphaMissense predicts likely benign (score 0.2189) — an in-silico prediction, not a clinical call.

DNAJC6 p.Thr899Ser

c.2696C>G · rs2101644706 · VCV1309326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2189 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2189	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -5.40	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 6	GERP 5.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 103 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	23.4	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 T842S vs ClinVar T899S) — 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.Thr899Ser
Coding: c.2696C>G
MANE Select: NM_001256864
dbSNP: rs2101644706
Type: single nucleotide variant
Location: chr1:65411311 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.29
Residue 899: the j domain

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

Similar variants

DNAJC6 p.Thr899= Likely benign ★★ same residue
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

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-thr899ser (accessed [today's date]).

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