Is DNAJB7 p.Arg12Lys (c.35G>A) pathogenic?

DNAJB7 p.Arg12Lys (c.35G>A) is classified Uncertain significance in DNAJB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely benign (0.1086); Very rare (popmax 0.00134%, afr).

How common is DNAJB7 p.Arg12Lys (c.35G>A) in the general population?

DNAJB7 p.Arg12Lys (c.35G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DNAJB7 p.Arg12Lys (c.35G>A)?

AlphaMissense predicts likely benign (score 0.1086) — an in-silico prediction, not a clinical call.

DNAJB7 p.Arg12Lys

c.35G>A · rs1487989123 · VCV2269693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1086	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.72	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 0.57	GERP 0.029, phastCons 0.98
Regional constraint	o/e 1.17	unconstrained · MANE · 926 bp · p 0.0012 · regional, not allelic
Overall
CADD	13.2	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 0.00134% African / African-American · 1/74,448 alleles

Overall 6.87e-05% 1/1,456,586 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: DNAJB7
Protein: p.Arg12Lys
Coding: c.35G>A
MANE Select: NM_145174
dbSNP: rs1487989123
Type: single nucleotide variant
Location: chr22:40861960 (GRCh38)
Gene constraint: LOEUF 1.85 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 59.38
Residue 12: the j domain

Full DNAJB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB7 p.Ala27Thr Uncertain significance ★ ⚠ same type
DNAJB7 p.Ala50Gly Uncertain significance ★ ⚠ same type
DNAJB7 p.Arg122Gly Uncertain significance ★ ⚠ same type
DNAJB7 p.Arg277Ser Uncertain significance ★ ⚠ same type
DNAJB7 p.Arg307Lys Uncertain significance ★ ⚠ same type
DNAJB7 p.Arg62Gln Uncertain significance ★ ⚠ same type
DNAJB7 p.Asn200Lys Uncertain significance ★ ⚠ same type
DNAJB7 p.Asn38Lys 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/dnajb7-p-arg12lys (accessed [today's date]).

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