Is DNAJC10 p.Cys301Phe (c.902G>T) pathogenic?

DNAJC10 p.Cys301Phe (c.902G>T) is classified Uncertain significance in DNAJC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely pathogenic (0.9749); Very rare (popmax 0.00178%, amr).

How common is DNAJC10 p.Cys301Phe (c.902G>T) in the general population?

DNAJC10 p.Cys301Phe (c.902G>T) is very rare (popmax 0.00178%, amr) (gnomAD).

What do computational predictors say about DNAJC10 p.Cys301Phe (c.902G>T)?

AlphaMissense predicts likely pathogenic (score 0.9749) — an in-silico prediction, not a clinical call.

DNAJC10 p.Cys301Phe

c.902G>T · VCV4013576

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9749 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9749	likely pathogenic · top 8% in DNAJC10
REVEL	0.456	indeterminate
SaProt	LLR -15.12	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 59 kb · p 0.087 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00178% Admixed American · 1/56,240 alleles

Overall 6.93e-05% 1/1,442,738 alleles · very rare

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.Cys301Phe
Coding: c.902G>T
MANE Select: NM_018981
Type: single nucleotide variant
Location: chr2:182736301 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.42
Residue 301: the 'trxb 1' region

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

Similar variants

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
DNAJC10 p.Arg361His 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-cys301phe (accessed [today's date]).

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