Is DNAJB13 p.Ala23Val (c.68C>T) pathogenic?

DNAJB13 p.Ala23Val (c.68C>T) is classified Uncertain significance in DNAJB13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-28). AlphaMissense: likely pathogenic (0.5764); Rare (popmax 0.231%, mid).

How common is DNAJB13 p.Ala23Val (c.68C>T) in the general population?

DNAJB13 p.Ala23Val (c.68C>T) is rare (popmax 0.231%, mid) (gnomAD).

What do computational predictors say about DNAJB13 p.Ala23Val (c.68C>T)?

AlphaMissense predicts likely pathogenic (score 0.5764) — an in-silico prediction, not a clinical call.

DNAJB13 p.Ala23Val

c.68C>T · rs185837848 · VCV2196057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5764 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.231%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5764	likely pathogenic
REVEL	0.403	indeterminate
SaProt	LLR -11.08	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.53	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 19 kb · p 0.47 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.231% Middle Eastern · 14/6,058 alleles

Filtering AF 0.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.00297% 48/1,614,050 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.231%	433
Remaining individualsnot grpmax-eligible	0.0064%	15,625
African / African-American	0.004%	25,023
European (non-Finnish)	0.00212%	47,201
Admixed American	0.00167%	60,026
Finnishnot grpmax-eligible	0.00156%	63,898

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.Ala23Val
Coding: c.68C>T
MANE Select: NM_153614
dbSNP: rs185837848
Type: single nucleotide variant
Location: chr11:73951137 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.81 · 1 PDB
Residue 23: the j domain

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-ala23val (accessed [today's date]).

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