Is DNAJB7 p.Glu41Asp (c.123A>T) pathogenic?

DNAJB7 p.Glu41Asp (c.123A>T) is classified Uncertain significance in DNAJB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-11). AlphaMissense: likely benign (0.2031); Very rare (popmax 0.00167%, amr).

How common is DNAJB7 p.Glu41Asp (c.123A>T) in the general population?

DNAJB7 p.Glu41Asp (c.123A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DNAJB7 p.Glu41Asp (c.123A>T)?

AlphaMissense predicts likely benign (score 0.2031) — an in-silico prediction, not a clinical call.

DNAJB7 p.Glu41Asp

c.123A>T · rs2057950978 · VCV2397093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2031 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2031	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -9.56	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 1.2	GERP 1.9, phastCons 0.99
Regional constraint	o/e 1.17	unconstrained · MANE · 926 bp · p 0.0012 · regional, not allelic
Overall
CADD	21.5	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 0.00167% Admixed American · 1/59,960 alleles

Overall 0.00131% 2/152,154 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,960
African / African-American	0.00133%	74,908

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.Glu41Asp
Coding: c.123A>T
MANE Select: NM_145174
dbSNP: rs2057950978
Type: single nucleotide variant
Location: chr22:40861872 (GRCh38)
Gene constraint: LOEUF 1.85 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 59.38
Residue 41: the j domain; a UniProt-annotated variant site (in)

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-glu41asp (accessed [today's date]).

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