Is DNAJB13 p.Phe232Ser (c.695T>C) pathogenic?

DNAJB13 p.Phe232Ser (c.695T>C) is classified Uncertain significance in DNAJB13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: ambiguous (0.4048); Very rare (popmax 0.00401%, afr).

How common is DNAJB13 p.Phe232Ser (c.695T>C) in the general population?

DNAJB13 p.Phe232Ser (c.695T>C) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about DNAJB13 p.Phe232Ser (c.695T>C)?

AlphaMissense predicts ambiguous (score 0.4048) — an in-silico prediction, not a clinical call.

DNAJB13 p.Phe232Ser

c.695T>C · VCV4013512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4048 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4048	ambiguous
REVEL	0.184	benign-leaning
SaProt	LLR -9.74	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 19 kb · p 0.47 · regional, not allelic
Overall
CADD	18.99	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 0.00401% African / African-American · 3/74,900 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,900 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: DNAJB13
Protein: p.Phe232Ser
Coding: c.695T>C
MANE Select: NM_153614
Type: single nucleotide variant
Location: chr11:73968433 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.81 · 1 PDB

Full DNAJB13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB13 p.Phe232= Likely benign ★ same residue
DNAJB13 p.Gln136Ter Pathogenic/Likely pathogenic ★★ same type
DNAJB13 p.Arg131Gln Uncertain significance ★★ ⚠ same type
DNAJB13 p.Arg142Gln Uncertain significance ★★ ⚠ same type
DNAJB13 p.Arg222Cys Uncertain significance ★★ ⚠ same type
DNAJB13 p.Arg301Cys Uncertain significance ★★ ⚠ same type
DNAJB13 p.Asn14Asp Uncertain significance ★★ ⚠ same type
DNAJB13 p.Asp169Gly 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/dnajb13-p-phe232ser (accessed [today's date]).

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