Is DNAJB11 p.Ala297Val (c.890C>T) pathogenic?

DNAJB11 p.Ala297Val (c.890C>T) is classified Uncertain significance in DNAJB11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-08). AlphaMissense: ambiguous (0.3856); Ultra-rare (popmax 0.0167%, mid).

How common is DNAJB11 p.Ala297Val (c.890C>T) in the general population?

DNAJB11 p.Ala297Val (c.890C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about DNAJB11 p.Ala297Val (c.890C>T)?

AlphaMissense predicts ambiguous (score 0.3856) — an in-silico prediction, not a clinical call.

DNAJB11 p.Ala297Val

c.890C>T · VCV3704378

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Computational evidence

Protein change
AlphaMissense	0.3856	ambiguous
REVEL	0.319	indeterminate
SaProt	LLR -9.95	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 15 kb · p 7.3e-05 · regional, not allelic
Overall
CADD	24.9	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 0.0167% Middle Eastern · 1/5,992 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00339%

Overall 0.00479% 76/1,588,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,992
African / African-American	0.00826%	12,102
Admixed American	0.00758%	13,191
East Asian	0.00688%	14,527
Remaining individualsnot grpmax-eligible	0.00488%	20,473
European (non-Finnish)	0.00478%	20,917
South Asian	0.0023%	43,445
Finnishnot grpmax-eligible	0.00157%	63,774

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: DNAJB11
Protein: p.Ala297Val
Coding: c.890C>T
MANE Select: NM_016306
Type: single nucleotide variant
Location: chr3:186584467 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.34
Residue 297: a UniProt-annotated variant site (in pkd6)

Full DNAJB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB11 p.Ala297= Likely benign ★ same residue
DNAJB11 p.Ala297fs Likely pathogenic ★ same residue
DNAJB11 p.Arg206Ter Pathogenic ★★ same type
DNAJB11 p.Arg242Ter Pathogenic ★★ same type
DNAJB11 p.Arg24Ter Pathogenic ★★ same type
DNAJB11 p.Arg34Ter Pathogenic ★★ same type
DNAJB11 p.Glu144Ter Pathogenic/Likely pathogenic ★★ same type
DNAJB11 p.Leu77Pro Likely pathogenic ★★ 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/dnajb11-p-ala297val (accessed [today's date]).

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