Is DNAJC28 p.Asp352Val (c.1055A>T) pathogenic?

DNAJC28 p.Asp352Val (c.1055A>T) is classified Uncertain significance in DNAJC28 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely benign (0.0886); Very rare (popmax 0.000767%, nfe).

How common is DNAJC28 p.Asp352Val (c.1055A>T) in the general population?

DNAJC28 p.Asp352Val (c.1055A>T) is very rare (popmax 0.000767%, nfe) (gnomAD).

What do computational predictors say about DNAJC28 p.Asp352Val (c.1055A>T)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

DNAJC28 p.Asp352Val

c.1055A>T · rs745998189 · VCV3084567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000767%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.98	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 0.89	GERP 4, phastCons 0.003
Regional constraint	o/e 0.97	unconstrained · MANE · 1,163 bp · p 0.54 · regional, not allelic
Overall
CADD	16.29	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 0.000767% European (non-Finnish) · 9/1,172,836 alleles

Filtering AF 0.000361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000262%

Overall 0.000568% 9/1,584,946 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: DNAJC28
Protein: p.Asp352Val
Coding: c.1055A>T
MANE Select: NM_001040192
dbSNP: rs745998189
Type: single nucleotide variant
Location: chr21:33488339 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 75.15

Full DNAJC28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC28 p.Arg134Gln Uncertain significance ★ ⚠ same type
DNAJC28 p.Arg202Cys Uncertain significance ★ ⚠ same type
DNAJC28 p.Arg202His Uncertain significance ★ ⚠ same type
DNAJC28 p.Arg310Gln Uncertain significance ★ ⚠ same type
DNAJC28 p.Arg310Gly Uncertain significance ★ ⚠ same type
DNAJC28 p.Asn378Asp Uncertain significance ★ ⚠ same type
DNAJC28 p.Asp329His Uncertain significance ★ ⚠ same type
DNAJC28 p.Asp88Asn 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/dnajc28-p-asp352val (accessed [today's date]).

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