Is DNAJA3 p.Leu443Phe (c.1327C>T) pathogenic?

DNAJA3 p.Leu443Phe (c.1327C>T) is classified Uncertain significance in DNAJA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.0841); Absent from gnomAD v4.1.

How common is DNAJA3 p.Leu443Phe (c.1327C>T) in the general population?

DNAJA3 p.Leu443Phe (c.1327C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJA3 p.Leu443Phe (c.1327C>T)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

DNAJA3 p.Leu443Phe

c.1327C>T · rs2506033826 · VCV3084364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,060)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.34	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 4	GERP -1.4, phastCons 0.66
Regional constraint	o/e 1.11	unconstrained · MANE · 29 kb · p 0.0067 · regional, not allelic
Overall
CADD	19.92	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

No allele count reported in gnomAD v4.1 (AN 1,608,060). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DNAJA3
Protein: p.Leu443Phe
Coding: c.1327C>T
MANE Select: NM_005147
dbSNP: rs2506033826
Type: single nucleotide variant
Location: chr16:4450485 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.04 · 4 PDB
Residue 443: the 'disordered' region

Full DNAJA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJA3 p.Ala112Val Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala21Thr Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala344Thr Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala355Val Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala357Thr Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala365Thr Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala3Val Uncertain significance ★ ⚠ same type
DNAJA3 p.Ala455Thr 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/dnaja3-p-leu443phe (accessed [today's date]).

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