Is DNAJB7 p.Val2Glu (c.5T>A) pathogenic?

DNAJB7 p.Val2Glu (c.5T>A) is classified Uncertain significance in DNAJB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.2688); Very rare (popmax 0.00364%, amr).

How common is DNAJB7 p.Val2Glu (c.5T>A) in the general population?

DNAJB7 p.Val2Glu (c.5T>A) is very rare (popmax 0.00364%, amr) (gnomAD).

What do computational predictors say about DNAJB7 p.Val2Glu (c.5T>A)?

AlphaMissense predicts likely benign (score 0.2688) — an in-silico prediction, not a clinical call.

DNAJB7 p.Val2Glu

c.5T>A · rs1391046954 · VCV2406297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2688 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2688	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -0.69, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 926 bp · p 0.0012 · regional, not allelic
Overall
CADD	23.1	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 0.00364% Admixed American · 2/54,886 alleles

Filtering AF 0.000604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000226%

Overall 0.000139% 2/1,436,136 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.Val2Glu
Coding: c.5T>A
MANE Select: NM_145174
dbSNP: rs1391046954
Type: single nucleotide variant
Location: chr22:40861990 (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-val2glu (accessed [today's date]).

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