Is DNAJB4 p.Ile171Arg (c.512T>G) pathogenic?

DNAJB4 p.Ile171Arg (c.512T>G) is classified Uncertain significance in DNAJB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely pathogenic (0.9891); Very rare (popmax 0.000169%, nfe).

How common is DNAJB4 p.Ile171Arg (c.512T>G) in the general population?

DNAJB4 p.Ile171Arg (c.512T>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about DNAJB4 p.Ile171Arg (c.512T>G)?

AlphaMissense predicts likely pathogenic (score 0.9891) — an in-silico prediction, not a clinical call.

DNAJB4 p.Ile171Arg

c.512T>G · VCV4243065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9891	likely pathogenic
REVEL	0.673	pathogenic-leaning
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 11 kb · p 7.2e-05 · regional, not allelic
Overall
CADD	26.2	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

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,030 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,884 alleles · very rare

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.Ile171Arg
Coding: c.512T>G
MANE Select: NM_007034
Type: single nucleotide variant
Location: chr1:78013351 (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.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-ile171arg (accessed [today's date]).

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