Is DNAJC4 p.Arg201Trp (c.601C>T) pathogenic?

DNAJC4 p.Arg201Trp (c.601C>T) is classified Uncertain significance in DNAJC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.6737); Ultra-rare (popmax 0.0167%, amr).

How common is DNAJC4 p.Arg201Trp (c.601C>T) in the general population?

DNAJC4 p.Arg201Trp (c.601C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about DNAJC4 p.Arg201Trp (c.601C>T)?

AlphaMissense predicts likely pathogenic (score 0.6737) — an in-silico prediction, not a clinical call.

DNAJC4 p.Arg201Trp

c.601C>T · rs754799881 · VCV2490190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6737 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6737	likely pathogenic
REVEL	0.154	moderately benign-leaning
SaProt	LLR -10.10	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -2.1, phastCons 0.75
Regional constraint	o/e 1.07	unconstrained · MANE · 3,326 bp · p 0.24 · regional, not allelic
Overall
CADD	21.0	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 0.0167% Admixed American · 10/60,034 alleles

Filtering AF 0.00899% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00123% 18/1,461,724 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,003
South Asian	0.0011%	91,084
European (non-Finnish)	0.000593%	168,574

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.Arg201Trp
Coding: c.601C>T
MANE Select: NM_005528
dbSNP: rs754799881
Type: single nucleotide variant
Location: chr11:64233967 (GRCh38)
Gene constraint: LOEUF 1.444 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.83

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.Arg203Pro 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-arg201trp (accessed [today's date]).

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