Is DNAJB4 p.Ser323Pro (c.967T>C) pathogenic?

DNAJB4 p.Ser323Pro (c.967T>C) is classified Uncertain significance in DNAJB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: likely benign (0.0873); Very rare (popmax 0.00223%, eas).

How common is DNAJB4 p.Ser323Pro (c.967T>C) in the general population?

DNAJB4 p.Ser323Pro (c.967T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DNAJB4 p.Ser323Pro (c.967T>C)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

DNAJB4 p.Ser323Pro

c.967T>C · VCV4013528

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.83	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 0.92	GERP -2.6, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 11 kb · p 7.2e-05 · regional, not allelic
Overall
CADD	15.11	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,872 alleles

Overall 0.000124% 2/1,614,016 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,872
African / African-American	0.00133%	74,932

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DNAJB4
Protein: p.Ser323Pro
Coding: c.967T>C
MANE Select: NM_007034
Type: single nucleotide variant
Location: chr1:78016200 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.68 (gnomAD)
Structure: AlphaFold pLDDT 83.43
Residue 323: a UniProt-annotated variant site (in cmyo21; severely decreased protein abundance in homozygous patient cells; increased degradation)

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.Arg146Ser 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

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-ser323pro (accessed [today's date]).

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