Is DNAJB14 p.Ser69Ile (c.206G>T) pathogenic?

DNAJB14 p.Ser69Ile (c.206G>T) is classified Uncertain significance in DNAJB14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-23). AlphaMissense: likely benign (0.081); Absent from gnomAD v4.1.

How common is DNAJB14 p.Ser69Ile (c.206G>T) in the general population?

DNAJB14 p.Ser69Ile (c.206G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJB14 p.Ser69Ile (c.206G>T)?

AlphaMissense predicts likely benign (score 0.081) — an in-silico prediction, not a clinical call.

DNAJB14 p.Ser69Ile

c.206G>T · VCV4013519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.081 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.081	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.55	GERP 0.83
Regional constraint	o/e 0.86	unconstrained · MANE · 23 kb · p 0.11 · regional, not allelic
Overall
CADD	15.71	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAJB14
Protein: p.Ser69Ile
Coding: c.206G>T
MANE Select: NM_001031723
Type: single nucleotide variant
Location: chr4:99930549 (GRCh38)
Gene constraint: LOEUF 0.64 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 76.45
Residue 69: the 'disordered' region

Full DNAJB14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB14 p.Ala43Gly Uncertain significance ★ ⚠ same type
DNAJB14 p.Arg350Cys Uncertain significance ★ ⚠ same type
DNAJB14 p.Arg350His Uncertain significance ★ ⚠ same type
DNAJB14 p.Arg355Gln Uncertain significance ★ ⚠ same type
DNAJB14 p.Arg371Gln Uncertain significance ★ ⚠ same type
DNAJB14 p.Arg64Gln Uncertain significance ★ ⚠ same type
DNAJB14 p.Arg64Leu Uncertain significance ★ ⚠ same type
DNAJB14 p.Asn327Asp 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/dnajb14-p-ser69ile (accessed [today's date]).

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