Is DNAJC13 p.Val459Ala (c.1376T>C) pathogenic?

DNAJC13 p.Val459Ala (c.1376T>C) is classified Uncertain significance in DNAJC13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.2866); Ultra-rare (popmax 0.0614%, afr).

How common is DNAJC13 p.Val459Ala (c.1376T>C) in the general population?

DNAJC13 p.Val459Ala (c.1376T>C) is ultra-rare (popmax 0.0614%, afr) (gnomAD).

What do computational predictors say about DNAJC13 p.Val459Ala (c.1376T>C)?

AlphaMissense predicts likely benign (score 0.2866) — an in-silico prediction, not a clinical call.

DNAJC13 p.Val459Ala

c.1376T>C · VCV3273067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2866 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0614%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2866	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -9.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 41 kb · p 7.6e-11 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0614% African / African-American · 46/74,962 alleles

Filtering AF 0.0472% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0423%

Overall 0.00341% 55/1,613,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0614%	1,630
Admixed American	0.01%	9,975
Remaining individualsnot grpmax-eligible	0.0048%	20,820

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: DNAJC13
Protein: p.Val459Ala
Coding: c.1376T>C
MANE Select: NM_015268
Type: single nucleotide variant
Location: chr3:132457295 (GRCh38)
Gene constraint: LOEUF 0.267 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.91

Full DNAJC13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC13 p.Arg677Trp Uncertain significance ★★ ⚠ same type
DNAJC13 p.Arg833Lys Uncertain significance ★★ ⚠ same type
DNAJC13 p.Ile2055Leu Uncertain significance ★★ ⚠ same type
DNAJC13 p.Leu1834Val Uncertain significance ★★ ⚠ same type
DNAJC13 p.Met688Val Uncertain significance ★★ ⚠ same type
DNAJC13 p.Thr66Met Uncertain significance ★★ ⚠ same type
DNAJC13 c.1349+102C>T Benign ★★ same type
DNAJC13 c.1349+103C>A Benign ★★ 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/dnajc13-p-val459ala (accessed [today's date]).

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