Is DNAJC9 p.Val68Ala (c.203T>C) pathogenic?

DNAJC9 p.Val68Ala (c.203T>C) is classified Uncertain significance in DNAJC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). AlphaMissense: likely pathogenic (0.6871); Very rare (popmax 0.00333%, amr).

How common is DNAJC9 p.Val68Ala (c.203T>C) in the general population?

DNAJC9 p.Val68Ala (c.203T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DNAJC9 p.Val68Ala (c.203T>C)?

AlphaMissense predicts likely pathogenic (score 0.6871) — an in-silico prediction, not a clinical call.

DNAJC9 p.Val68Ala

c.203T>C · rs761360885 · VCV2261977

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6871 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6871	likely pathogenic
REVEL	0.435	indeterminate
SaProt	LLR -12.31	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 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 3,786 bp · p 0.51 · regional, not allelic
Overall
CADD	24.3	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 0.00333% Admixed American · 2/60,002 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00118% 19/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,001
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00136%	73,750

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: DNAJC9
Protein: p.Val68Ala
Coding: c.203T>C
MANE Select: NM_015190
dbSNP: rs761360885
Type: single nucleotide variant
Location: chr10:73246806 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.67 · 2 PDB
Residue 68: the j domain

Full DNAJC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FAM149B1 p.Pro463Leu Uncertain significance ★★ ⚠ same type
FAM149B1 p.Arg395Ter Likely pathogenic ★ same type
FAM149B1 p.Arg400Ter Pathogenic ★ same type
FAM149B1 p.Arg468Ter Likely pathogenic ★ same type
DNAJC9 p.Arg24Leu Uncertain significance ★ ⚠ same type
DNAJC9 p.Arg46Leu Uncertain significance ★ ⚠ same type
DNAJC9 p.Asp112Gly Uncertain significance ★ ⚠ same type
DNAJC9 p.Gln132Glu 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/dnajc9-p-val68ala (accessed [today's date]).

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