Is DNAJC19 p.Ser46Ile (c.137G>T) pathogenic?

DNAJC19 p.Ser46Ile (c.137G>T) is classified Uncertain significance in DNAJC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-25). AlphaMissense: ambiguous (0.3665); Absent from gnomAD v4.1.

How common is DNAJC19 p.Ser46Ile (c.137G>T) in the general population?

DNAJC19 p.Ser46Ile (c.137G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJC19 p.Ser46Ile (c.137G>T)?

AlphaMissense predicts ambiguous (score 0.3665) — an in-silico prediction, not a clinical call.

DNAJC19 p.Ser46Ile

c.137G>T · rs2473930439 · VCV1703376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3665 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3665	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -10.73	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 4,959 bp · p 0.0025 · regional, not allelic
Overall
CADD	24.1	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

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: DNAJC19
Protein: p.Ser46Ile
Coding: c.137G>T
MANE Select: NM_145261
dbSNP: rs2473930439
Type: single nucleotide variant
Location: chr3:180987015 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50

Full DNAJC19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC19 p.Ser46Gly Uncertain significance ★ ⚠ same residue
DNAJC19 c.130-1G>C Pathogenic ★★ same type
DNAJC19 c.4-1G>A Likely pathogenic ★★ same type
DNAJC19 c.55+1G>A Pathogenic/Likely pathogenic ★★ same type
DNAJC19 p.Ala25Thr Uncertain significance ★★ ⚠ same type
DNAJC19 p.Ala73Thr Uncertain significance ★★ same type
DNAJC19 p.Arg20Cys Uncertain significance ★★ ⚠ same type
DNAJC19 p.Arg84Gln 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/dnajc19-p-ser46ile (accessed [today's date]).

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