Is DNAJC4 p.Arg100His (c.299G>A) pathogenic?

DNAJC4 p.Arg100His (c.299G>A) is classified Uncertain significance in DNAJC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). AlphaMissense: likely benign (0.0775); Very rare (popmax 0.00475%, nfe).

How common is DNAJC4 p.Arg100His (c.299G>A) in the general population?

DNAJC4 p.Arg100His (c.299G>A) is very rare (popmax 0.00475%, nfe) (gnomAD).

What do computational predictors say about DNAJC4 p.Arg100His (c.299G>A)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

DNAJC4 p.Arg100His

c.299G>A · rs760961158 · VCV2516065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00475%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -10.60	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 0.41	GERP -3.2
Regional constraint	o/e 1.07	unconstrained · MANE · 3,326 bp · p 0.24 · regional, not allelic
Overall
CADD	12.46	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 0.00475% European (non-Finnish) · 56/1,179,146 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00409% 66/1,612,738 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0237%	4,221
European (non-Finnish)grpmax	0.00475%	21,056
Finnishnot grpmax-eligible	0.00313%	32,000
East Asian	0.00223%	44,852

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg100His
Coding: c.299G>A
MANE Select: NM_005528
dbSNP: rs760961158
Type: single nucleotide variant
Location: chr11:64232548 (GRCh38)
Gene constraint: LOEUF 1.444 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.83
Residue 100: the 'disordered' region

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

Similar variants

DNAJC4 p.Arg100Cys Uncertain significance ★ ⚠ same residue
DNAJC4 p.Ala200Asp Uncertain significance ★ ⚠ same type
DNAJC4 p.Ala204Pro Uncertain significance ★ ⚠ same type
DNAJC4 p.Ala26Thr 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
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-arg100his (accessed [today's date]).

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