Is DNAJA4 p.Ile188Val (c.562A>G) pathogenic?

DNAJA4 p.Ile188Val (c.562A>G) is classified Uncertain significance in DNAJA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.1321); Rare (popmax 0.51%, afr).

How common is DNAJA4 p.Ile188Val (c.562A>G) in the general population?

DNAJA4 p.Ile188Val (c.562A>G) is rare (popmax 0.51%, afr) (gnomAD).

What do computational predictors say about DNAJA4 p.Ile188Val (c.562A>G)?

AlphaMissense predicts likely benign (score 0.1321) — an in-silico prediction, not a clinical call.

DNAJA4 p.Ile188Val

c.562A>G · VCV4661231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1321 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.51%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1321	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -10.84	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 16 kb · p 0.0033 · regional, not allelic
Overall
CADD	21.4	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 0.51% African / African-American · 383/75,050 alleles

Filtering AF 0.468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.452%

Overall 0.0276% 446/1,614,202 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.51%	196
Remaining individualsnot grpmax-eligible	0.0384%	2,605
Admixed American	0.03%	3,334
South Asian	0.0022%	45,541
European (non-Finnish)	0.00161%	62,108

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: DNAJA4
Protein: p.Ile188Val
Coding: c.562A>G
MANE Select: NM_001130182
Type: single nucleotide variant
Location: chr15:78274340 (GRCh38)
Gene constraint: LOEUF 1.024 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.76

Full DNAJA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJA4 p.Ala25Val Uncertain significance ★ ⚠ same type
DNAJA4 p.Ala314Val Uncertain significance ★ ⚠ same type
DNAJA4 p.Arg157Trp Uncertain significance ★ ⚠ same type
DNAJA4 p.Arg187Cys Uncertain significance ★ ⚠ same type
DNAJA4 p.Arg193Leu Uncertain significance ★ ⚠ same type
DNAJA4 p.Arg255Gln Uncertain significance ★ ⚠ same type
DNAJA4 p.Arg305Cys Uncertain significance ★ ⚠ same type
DNAJA4 p.Arg350Gly 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/dnaja4-p-ile188val (accessed [today's date]).

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