Is DNAJB11 p.Phe322Ile (c.964T>A) pathogenic?

DNAJB11 p.Phe322Ile (c.964T>A) is classified Conflicting classifications of pathogenicity in DNAJB11 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-01). AlphaMissense: ambiguous (0.5278); Ultra-rare (popmax 0.0162%, amr); Associated with Inborn genetic diseases.

What condition is associated with DNAJB11 p.Phe322Ile (c.964T>A)?

DNAJB11 p.Phe322Ile (c.964T>A) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJB11 p.Phe322Ile (c.964T>A) in the general population?

DNAJB11 p.Phe322Ile (c.964T>A) is ultra-rare (popmax 0.0162%, amr) (gnomAD).

What do computational predictors say about DNAJB11 p.Phe322Ile (c.964T>A)?

AlphaMissense predicts ambiguous (score 0.5278) — an in-silico prediction, not a clinical call.

DNAJB11 p.Phe322Ile

c.964T>A · VCV4243040

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5278 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0162%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5278	ambiguous
REVEL	0.769	pathogenic-leaning
SaProt	LLR -12.21	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 15 kb · p 7.3e-05 · regional, not allelic
Overall
CADD	25.1	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 0.0162% Admixed American · 9/55,670 alleles

Filtering AF 0.00838% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00628%

Overall 0.000691% 10/1,447,298 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0162%	6,186
Remaining individualsnot grpmax-eligible	0.00162%	61,902

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.Phe322Ile
Coding: c.964T>A
MANE Select: NM_016306
Type: single nucleotide variant
Location: chr3:186584541 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.34
Residue 322: a UniProt-annotated variant site (in pkd6)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAJB11 p.Arg289Trp Uncertain significance ★★ ⚠ same condition
DNAJB11 p.Thr188Ser Uncertain significance ★★ ⚠ same condition
DNAJB11 p.Thr8Ile Uncertain significance ★★ ⚠ same condition
DNAJB11 p.Ala147Val Uncertain significance ★ ⚠ same condition
DNAJB11 p.Ala163Ser Uncertain significance ★ ⚠ same condition
DNAJB11 p.Ala19Val Uncertain significance ★ ⚠ same condition
DNAJB11 p.Arg167Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
DNAJB11 p.Arg176Gln Uncertain significance ★ ⚠ same condition

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-phe322ile (accessed [today's date]).

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