Is DNAJC10 p.Ile18Leu (c.52A>C) pathogenic?

DNAJC10 p.Ile18Leu (c.52A>C) is classified Uncertain significance in DNAJC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). AlphaMissense: likely benign (0.0587); Ultra-rare (popmax 0.0153%, nfe).

How common is DNAJC10 p.Ile18Leu (c.52A>C) in the general population?

DNAJC10 p.Ile18Leu (c.52A>C) is ultra-rare (popmax 0.0153%, nfe) (gnomAD).

What do computational predictors say about DNAJC10 p.Ile18Leu (c.52A>C)?

AlphaMissense predicts likely benign (score 0.0587) — an in-silico prediction, not a clinical call.

DNAJC10 p.Ile18Leu

c.52A>C · rs769542885 · VCV2246887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0587 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0153%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0587	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -5.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.77	GERP -4.5
Regional constraint	o/e 1.06	unconstrained · MANE · 59 kb · p 0.087 · regional, not allelic
Overall
CADD	0.363	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0153% European (non-Finnish) · 181/1,179,666 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.0125% 202/1,613,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0153%	6,518
South Asian	0.0132%	7,574
Remaining individualsnot grpmax-eligible	0.00801%	12,484
Admixed American	0.00334%	29,981
African / African-American	0.00267%	37,461

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: DNAJC10
Protein: p.Ile18Leu
Coding: c.52A>C
MANE Select: NM_018981
dbSNP: rs769542885
Type: single nucleotide variant
Location: chr2:182718138 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.42

Full DNAJC10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC10 p.Ile18Val Uncertain significance ★ ⚠ same residue
DNAJC10 p.Ala697Pro Uncertain significance ★★ ⚠ same type
DNAJC10 p.Ala730Thr Uncertain significance ★ ⚠ same type
DNAJC10 p.Ala772Ser Uncertain significance ★ ⚠ same type
DNAJC10 p.Arg119Cys Uncertain significance ★ ⚠ same type
DNAJC10 p.Arg119His Uncertain significance ★ ⚠ same type
DNAJC10 p.Arg16Met Uncertain significance ★ ⚠ same type
DNAJC10 p.Arg208Gln 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/dnajc10-p-ile18leu (accessed [today's date]).

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