Is DNAJB14 p.Tyr324Phe (c.971A>T) pathogenic?

DNAJB14 p.Tyr324Phe (c.971A>T) is classified Uncertain significance in DNAJB14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.0978); Absent from gnomAD v4.1.

How common is DNAJB14 p.Tyr324Phe (c.971A>T) in the general population?

DNAJB14 p.Tyr324Phe (c.971A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJB14 p.Tyr324Phe (c.971A>T)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

DNAJB14 p.Tyr324Phe

c.971A>T · VCV4661268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.372	indeterminate
SaProt	LLR -9.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.8, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 7,772 bp · p 4.7e-06 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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.Tyr324Phe
Coding: c.971A>T
MANE Select: NM_001031723
Type: single nucleotide variant
Location: chr4:99903770 (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-tyr324phe (accessed [today's date]).

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