Is DNAJB4 p.Arg146Ser (c.438G>C) pathogenic?

DNAJB4 p.Arg146Ser (c.438G>C) is classified Uncertain significance in DNAJB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: ambiguous (0.4294); Absent from gnomAD v4.1.

How common is DNAJB4 p.Arg146Ser (c.438G>C) in the general population?

DNAJB4 p.Arg146Ser (c.438G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJB4 p.Arg146Ser (c.438G>C)?

AlphaMissense predicts ambiguous (score 0.4294) — an in-silico prediction, not a clinical call.

DNAJB4 p.Arg146Ser

c.438G>C · rs2524285880 · VCV2330268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4294 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4294	ambiguous
REVEL	0.195	benign-leaning
SaProt	LLR -5.97	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 11 kb · p 7.2e-05 · regional, not allelic
Overall
CADD	18.23	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: DNAJB4
Protein: p.Arg146Ser
Coding: c.438G>C
MANE Select: NM_007034
dbSNP: rs2524285880
Type: single nucleotide variant
Location: chr1:78013277 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.68 (gnomAD)
Structure: AlphaFold pLDDT 83.43

Full DNAJB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB4 p.Ala76Pro Uncertain significance ★ ⚠ same type
DNAJB4 p.Arg153His Uncertain significance ★ ⚠ same type
DNAJB4 p.Arg178Gln Uncertain significance ★ ⚠ same type
DNAJB4 p.Arg245Ser Uncertain significance ★ ⚠ same type
DNAJB4 p.Arg292Ile Uncertain significance ★ ⚠ same type
DNAJB4 p.Asp239Tyr Uncertain significance ★ ⚠ same type
DNAJB4 p.Gln40Glu Uncertain significance ★ ⚠ same type
DNAJB4 p.Glu18Asp 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/dnajb4-p-arg146ser (accessed [today's date]).

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