Is DNAJB7 p.Cys84Arg (c.250T>C) pathogenic?

DNAJB7 p.Cys84Arg (c.250T>C) is classified Uncertain significance in DNAJB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely benign (0.0844); Ultra-rare (popmax 0.0164%, mid).

How common is DNAJB7 p.Cys84Arg (c.250T>C) in the general population?

DNAJB7 p.Cys84Arg (c.250T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DNAJB7 p.Cys84Arg (c.250T>C)?

AlphaMissense predicts likely benign (score 0.0844) — an in-silico prediction, not a clinical call.

DNAJB7 p.Cys84Arg

c.250T>C · rs200291636 · VCV2380467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0844 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0844	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -6.24	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 2	GERP -0.69, phastCons 0.32
Regional constraint	o/e 1.17	unconstrained · MANE · 926 bp · p 0.0012 · regional, not allelic
Overall
CADD	5.89	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.0106% 171/1,613,398 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.426%	235
Remaining individualsnot grpmax-eligible	0.032%	3,122
Middle Easterngrpmax	0.0164%	6,082
European (non-Finnish)	0.00195%	51,299
Admixed American	0.00167%	59,834

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys84Arg
Coding: c.250T>C
MANE Select: NM_145174
dbSNP: rs200291636
Type: single nucleotide variant
Location: chr22:40861745 (GRCh38)
Gene constraint: LOEUF 1.85 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 59.38

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.Arg12Lys 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

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-cys84arg (accessed [today's date]).

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