Is DNAJC3 p.Val306Ile (c.916G>A) pathogenic?

DNAJC3 p.Val306Ile (c.916G>A) is classified Likely benign in DNAJC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0654); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with DNAJC3 p.Val306Ile (c.916G>A)?

DNAJC3 p.Val306Ile (c.916G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJC3 p.Val306Ile (c.916G>A) in the general population?

DNAJC3 p.Val306Ile (c.916G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DNAJC3 p.Val306Ile (c.916G>A)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

DNAJC3 p.Val306Ile

c.916G>A · VCV4617718

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.041	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 -5.1	GERP -5.6
Regional constraint	o/e 0.89	unconstrained · MANE · 114 kb · p 0.0067 · regional, not allelic
Overall
CADD	0.004	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 0.0011% South Asian · 1/91,064 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,704 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,064
European (non-Finnish)	0.000254%	393,311

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: DNAJC3
Protein: p.Val306Ile
Coding: c.916G>A
MANE Select: NM_006260
Type: single nucleotide variant
Location: chr13:95763710 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.78 · 2 PDB
Residue 306: an α-helix

Full DNAJC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAJC3 p.Leu231Val Uncertain significance ★★ ⚠ same condition
DNAJC3 p.Thr171Ile Uncertain significance ★★ ⚠ same condition
DNAJC3 p.Ala164Ser Uncertain significance ★ ⚠ same condition
DNAJC3 p.Ala224Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
DNAJC3 p.Ala325Thr Uncertain significance ★ ⚠ same condition
DNAJC3 p.Ala366Gly Uncertain significance ★ ⚠ same condition
DNAJC3 p.Arg10Gln Uncertain significance ★ ⚠ same condition
DNAJC3 p.Arg156Cys Uncertain significance ★ ⚠ same condition

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/dnajc3-p-val306ile (accessed [today's date]).

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