Is DNAJB9 p.Phe113Ser (c.338T>C) pathogenic?

DNAJB9 p.Phe113Ser (c.338T>C) is classified Uncertain significance in DNAJB9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.8403); Very rare (popmax 0.00267%, afr).

How common is DNAJB9 p.Phe113Ser (c.338T>C) in the general population?

DNAJB9 p.Phe113Ser (c.338T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DNAJB9 p.Phe113Ser (c.338T>C)?

AlphaMissense predicts likely pathogenic (score 0.8403) — an in-silico prediction, not a clinical call.

DNAJB9 p.Phe113Ser

c.338T>C · VCV4833800

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8403 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8403	likely pathogenic
REVEL	0.58	indeterminate
SaProt	LLR -10.77	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 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,623 bp · p 0.5 · regional, not allelic
Overall
CADD	27.9	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 0.00267% African / African-American · 2/74,922 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,966 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: DNAJB9
Protein: p.Phe113Ser
Coding: c.338T>C
MANE Select: NM_012328
Type: single nucleotide variant
Location: chr7:108573019 (GRCh38)
Gene constraint: LOEUF 0.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.62 · 1 PDB
Residue 113: the 'divergent targeting domain' region

Full DNAJB9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB9 p.Arg136His Benign ★★ same type
DNAJB9 p.Ala45Thr Uncertain significance ★ ⚠ same type
DNAJB9 p.Ala63Val Uncertain significance ★ ⚠ same type
DNAJB9 p.Ala80Asp Uncertain significance ★ ⚠ same type
DNAJB9 p.Arg101Gly Uncertain significance ★ ⚠ same type
DNAJB9 p.Arg144Cys Uncertain significance ★ ⚠ same type
DNAJB9 p.Arg82Gly Uncertain significance ★ ⚠ same type
DNAJB9 p.Asn81Asp 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/dnajb9-p-phe113ser (accessed [today's date]).

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