Is DNAJA4 p.Val243Met (c.727G>A) pathogenic?

DNAJA4 p.Val243Met (c.727G>A) is classified Uncertain significance in DNAJA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-31). AlphaMissense: ambiguous (0.3516); Very rare (popmax 0.00833%, amr).

How common is DNAJA4 p.Val243Met (c.727G>A) in the general population?

DNAJA4 p.Val243Met (c.727G>A) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about DNAJA4 p.Val243Met (c.727G>A)?

AlphaMissense predicts ambiguous (score 0.3516) — an in-silico prediction, not a clinical call.

DNAJA4 p.Val243Met

c.727G>A · rs747222954 · VCV2293301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3516 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Computational evidence

Protein change
AlphaMissense	0.3516	ambiguous
REVEL	0.433	indeterminate
SaProt	LLR -7.09	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 16 kb · p 0.0033 · regional, not allelic
Overall
CADD	28.0	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 0.00833% Admixed American · 5/60,032 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.00041% 6/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,006
European (non-Finnish)	8.47e-05%	1,180,030

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.Val243Met
Coding: c.727G>A
MANE Select: NM_001130182
dbSNP: rs747222954
Type: single nucleotide variant
Location: chr15:78275578 (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-val243met (accessed [today's date]).

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