Is DNAJA2 p.Ser153Pro (c.457T>C) pathogenic?

DNAJA2 p.Ser153Pro (c.457T>C) is classified Uncertain significance in DNAJA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.0674); Absent from gnomAD v4.1.

How common is DNAJA2 p.Ser153Pro (c.457T>C) in the general population?

DNAJA2 p.Ser153Pro (c.457T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJA2 p.Ser153Pro (c.457T>C)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

DNAJA2 p.Ser153Pro

c.457T>C · rs2549002547 · VCV3084359

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -5.02	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 5.1	phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 17 kb · p 8e-14 · regional, not allelic
Overall
CADD	19.78	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

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: DNAJA2
Protein: p.Ser153Pro
Coding: c.457T>C
MANE Select: NM_005880
dbSNP: rs2549002547
Type: single nucleotide variant
Location: chr16:46967633 (GRCh38)
Gene constraint: LOEUF 0.258 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 1 PDB

Full DNAJA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJA2 p.Gly79Ser Uncertain significance ★★ ⚠ same type
DNAJA2 p.Arg107Gln Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg110Gly Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg112Gly Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg165Gln Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg201Ser Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg388His Uncertain significance ★ ⚠ same type
DNAJA2 p.Arg68Lys 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/dnaja2-p-ser153pro (accessed [today's date]).

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