Is DNAJB13 p.Phe294= (c.882C>T) pathogenic?

DNAJB13 p.Phe294= (c.882C>T) is classified Benign in DNAJB13 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 36.7%, amr) — too common for a highly-penetrant pathogenic allele.

DNAJB13 p.Phe294=

Q: How common is DNAJB13 p.Phe294= (c.882C>T) in the general population?

DNAJB13 p.Phe294= (c.882C>T) is common (popmax 36.7%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.882C>T · rs2306819 · VCV1253105

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 36.7%, amr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.5	GERP -8.3
Overall
CADD	4.299	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.7% Admixed American · 21,745/59,286 alleles

Filtering AF 36.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.1%

Overall 28.9% 464,579/1,609,274 alleles · common exomes 422,136/1,457,280 · genomes 42,443/151,994 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	37.4%	3
Admixed Americangrpmax	36.7%	3
Middle Eastern	32.9%	3
Finnishnot grpmax-eligible	30.5%	3
European (non-Finnish)	29.7%	3
Ashkenazi Jewishnot grpmax-eligible	29.5%	3
Remaining individualsnot grpmax-eligible	28.1%	4
South Asian	22.7%	4
African / African-American	21.6%	5
East Asian	17.4%	6

Amish 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: DNAJB13
Protein: p.Phe294=
Coding: c.882C>T
MANE Select: NM_153614
dbSNP: rs2306819
Type: single nucleotide variant
Location: chr11:73970045 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.81 · 1 PDB

Full DNAJB13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB13 p.Gln136Ter Pathogenic/Likely pathogenic ★★ same type
DNAJB13 p.Arg131Gln Uncertain significance ★★ ⚠ same type
DNAJB13 p.Arg142Gln Uncertain significance ★★ ⚠ same type
DNAJB13 p.Arg222Cys Uncertain significance ★★ ⚠ same type
DNAJB13 p.Arg301Cys Uncertain significance ★★ ⚠ same type
DNAJB13 p.Asn14Asp Uncertain significance ★★ ⚠ same type
DNAJB13 p.Asp169Gly Uncertain significance ★★ same type
DNAJB13 p.Asp65Asn 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/dnajb13-p-phe294 (accessed [today's date]).

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