Is DNAJC4 p.Pro70Arg (c.209C>G) pathogenic?

DNAJC4 p.Pro70Arg (c.209C>G) is classified Uncertain significance in DNAJC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: ambiguous (0.3464); Ultra-rare (popmax 0.0288%, amr).

How common is DNAJC4 p.Pro70Arg (c.209C>G) in the general population?

DNAJC4 p.Pro70Arg (c.209C>G) is ultra-rare (popmax 0.0288%, amr) (gnomAD).

What do computational predictors say about DNAJC4 p.Pro70Arg (c.209C>G)?

AlphaMissense predicts ambiguous (score 0.3464) — an in-silico prediction, not a clinical call.

DNAJC4 p.Pro70Arg

c.209C>G · VCV3841584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3464 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0288%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3464	ambiguous
REVEL	0.188	benign-leaning
SaProt	LLR -8.57	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,326 bp · p 0.24 · regional, not allelic
Overall
CADD	26.5	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 0.0288% Admixed American · 17/59,128 alleles

Filtering AF 0.0182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0149%

Overall 0.00537% 86/1,600,756 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0288%	3,478
African / African-American	0.0214%	4,670
European (non-Finnish)	0.00435%	22,963
Remaining individualsnot grpmax-eligible	0.00324%	30,911

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: DNAJC4
Protein: p.Pro70Arg
Coding: c.209C>G
MANE Select: NM_005528
Type: single nucleotide variant
Location: chr11:64232458 (GRCh38)
Gene constraint: LOEUF 1.444 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.83
Residue 70: the j domain

Full DNAJC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC4 p.Ala200Asp Uncertain significance ★ ⚠ same type
DNAJC4 p.Ala204Pro Uncertain significance ★ ⚠ same type
DNAJC4 p.Ala26Thr Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg100Cys Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg100His Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg109Pro Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg15Gly Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg201Trp 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/dnajc4-p-pro70arg (accessed [today's date]).

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