Is DNAJB14 p.Val100Ile (c.298G>A) pathogenic?

DNAJB14 p.Val100Ile (c.298G>A) is classified Uncertain significance in DNAJB14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). AlphaMissense: ambiguous (0.3479); Very rare (popmax 8.55e-05%, nfe).

How common is DNAJB14 p.Val100Ile (c.298G>A) in the general population?

DNAJB14 p.Val100Ile (c.298G>A) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

What do computational predictors say about DNAJB14 p.Val100Ile (c.298G>A)?

AlphaMissense predicts ambiguous (score 0.3479) — an in-silico prediction, not a clinical call.

DNAJB14 p.Val100Ile

c.298G>A · rs1373243869 · VCV2536684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3479 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3479	ambiguous
REVEL	0.186	benign-leaning
SaProt	LLR -11.66	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 23 kb · p 0.11 · regional, not allelic
Overall
CADD	23.9	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 8.55e-05% European (non-Finnish) · 1/1,169,876 alleles

Overall 6.95e-05% 1/1,439,516 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: DNAJB14
Protein: p.Val100Ile
Coding: c.298G>A
MANE Select: NM_001031723
dbSNP: rs1373243869
Type: single nucleotide variant
Location: chr4:99930457 (GRCh38)
Gene constraint: LOEUF 0.64 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 76.45

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-val100ile (accessed [today's date]).

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