Is DNAJB1 p.Pro232Ala (c.694C>G) pathogenic?

DNAJB1 p.Pro232Ala (c.694C>G) is classified Uncertain significance in DNAJB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: ambiguous (0.3863); Very rare (popmax 0.00439%, sas).

How common is DNAJB1 p.Pro232Ala (c.694C>G) in the general population?

DNAJB1 p.Pro232Ala (c.694C>G) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about DNAJB1 p.Pro232Ala (c.694C>G)?

AlphaMissense predicts ambiguous (score 0.3863) — an in-silico prediction, not a clinical call.

DNAJB1 p.Pro232Ala

c.694C>G · VCV4013496

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3863 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3863	ambiguous
REVEL	0.722	pathogenic-leaning
SaProt	LLR -7.35	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 2,406 bp · p 0.0059 · regional, not allelic
Overall
CADD	27.2	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 0.00439% South Asian · 4/91,084 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,614,074 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: DNAJB1
Protein: p.Pro232Ala
Coding: c.694C>G
MANE Select: NM_006145
Type: single nucleotide variant
Location: chr19:14516564 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.71 · 15 PDB
Residue 232: an α-helix

Full DNAJB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB1 p.Asn272= Benign ★★ same type
DNAJB1 p.Val288= Benign ★★ same type
DNAJB1 p.Ala265Val Uncertain significance ★ ⚠ same type
DNAJB1 p.Arg119Gln Uncertain significance ★ ⚠ same type
DNAJB1 p.Arg13Cys Uncertain significance ★ ⚠ same type
DNAJB1 p.Arg26Leu Uncertain significance ★ ⚠ same type
DNAJB1 p.Arg290Ser Uncertain significance ★ ⚠ same type
DNAJB1 p.Arg294Trp 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/dnajb1-p-pro232ala (accessed [today's date]).

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