Is DNAJC1 p.Leu451Pro (c.1352T>C) pathogenic?

DNAJC1 p.Leu451Pro (c.1352T>C) is classified Likely benign in DNAJC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-21). AlphaMissense: likely benign (0.039); Absent from gnomAD v4.1.

How common is DNAJC1 p.Leu451Pro (c.1352T>C) in the general population?

DNAJC1 p.Leu451Pro (c.1352T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJC1 p.Leu451Pro (c.1352T>C)?

AlphaMissense predicts likely benign (score 0.039) — an in-silico prediction, not a clinical call.

DNAJC1 p.Leu451Pro

c.1352T>C · rs2492915419 · VCV2284580

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.039 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.039	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.59	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 0.37	GERP -2.4
Regional constraint	o/e 1.02	unconstrained · MANE · 247 kb · p 0.65 · regional, not allelic
Overall
CADD	1.359	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAJC1
Protein: p.Leu451Pro
Coding: c.1352T>C
MANE Select: NM_022365
dbSNP: rs2492915419
Type: single nucleotide variant
Location: chr10:21759414 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.45 · 2 PDB
Residue 451: the 'disordered' region

Full DNAJC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC1 p.Ala263Ser Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala3Thr Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala417Gly Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala455Val Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala490Gly Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala524Ser Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala537Thr Uncertain significance ★ ⚠ same type
DNAJC1 p.Arg107Thr 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/dnajc1-p-leu451pro (accessed [today's date]).

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