Is DNAJC30 p.Leu50Pro (c.149T>C) pathogenic?

DNAJC30 p.Leu50Pro (c.149T>C) is classified Uncertain significance in DNAJC30 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-09). AlphaMissense: ambiguous (0.48); Very rare (popmax 0.004%, afr).

How common is DNAJC30 p.Leu50Pro (c.149T>C) in the general population?

DNAJC30 p.Leu50Pro (c.149T>C) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about DNAJC30 p.Leu50Pro (c.149T>C)?

AlphaMissense predicts ambiguous (score 0.48) — an in-silico prediction, not a clinical call.

DNAJC30 p.Leu50Pro

c.149T>C · rs374961753 · VCV2546115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.48 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Computational evidence

Protein change
AlphaMissense	0.48	ambiguous
REVEL	0.304	indeterminate
SaProt	LLR -11.57	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 7.3, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 677 bp · p 0.083 · regional, not allelic
Overall
CADD	26.1	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 0.004% African / African-American · 3/74,958 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,982 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: DNAJC30
Protein: p.Leu50Pro
Coding: c.149T>C
MANE Select: NM_032317
dbSNP: rs374961753
Type: single nucleotide variant
Location: chr7:73683275 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.87 · 1 PDB
Residue 50: an α-helix; the j domain

Full DNAJC30 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC30 p.Tyr51Cys Pathogenic/Likely pathogenic ★★ same type
DNAJC30 p.Gly34Arg Benign ★★ same type
DNAJC30 p.Trp8Ter Likely pathogenic ★ same type
DNAJC30 p.Tyr98Ser Likely pathogenic ★ same type
DNAJC30 c.*122C>T Uncertain significance ★ same type
DNAJC30 p.Ala153Ser Uncertain significance ★ ⚠ same type
DNAJC30 p.Ala157Val Uncertain significance ★ ⚠ same type
DNAJC30 p.Ala20Val 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/dnajc30-p-leu50pro (accessed [today's date]).

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