Is DNAJC5B p.Arg11Trp (c.31C>T) pathogenic?

DNAJC5B p.Arg11Trp (c.31C>T) is classified Uncertain significance in DNAJC5B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: ambiguous (0.4591); Very rare (popmax 0.0044%, sas).

How common is DNAJC5B p.Arg11Trp (c.31C>T) in the general population?

DNAJC5B p.Arg11Trp (c.31C>T) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about DNAJC5B p.Arg11Trp (c.31C>T)?

AlphaMissense predicts ambiguous (score 0.4591) — an in-silico prediction, not a clinical call.

DNAJC5B p.Arg11Trp

c.31C>T · VCV4243313

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4591 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Computational evidence

Protein change
AlphaMissense	0.4591	ambiguous
REVEL	0.633	indeterminate
SaProt	LLR -13.48	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP 1.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 48 kb · p 0.85 · regional, not allelic
Overall
CADD	25.8	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 0.0044% South Asian · 4/91,008 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00212% 31/1,461,550 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,752
Remaining individualsnot grpmax-eligible	0.0032%	31,247
East Asian	0.00223%	44,870
European (non-Finnish)	0.00203%	49,163

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: DNAJC5B
Protein: p.Arg11Trp
Coding: c.31C>T
MANE Select: NM_033105
Type: single nucleotide variant
Location: chr8:66051578 (GRCh38)
Gene constraint: LOEUF 1.356 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.07

Full DNAJC5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC5B p.Ala19Val Uncertain significance ★ ⚠ same type
DNAJC5B p.Cys127Ser Uncertain significance ★ ⚠ same type
DNAJC5B p.Glu143Ter Uncertain significance ★ same type
DNAJC5B p.Glu160Asp Uncertain significance ★ ⚠ same type
DNAJC5B p.Gly118Val Uncertain significance ★ ⚠ same type
DNAJC5B p.Gly87Val Uncertain significance ★ ⚠ same type
DNAJC5B p.Ile5Met Uncertain significance ★ ⚠ same type
DNAJC5B p.Ile64Ser 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/dnajc5b-p-arg11trp (accessed [today's date]).

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