Is DNAJC2 p.Phe551Leu (c.1653C>G) pathogenic?

DNAJC2 p.Phe551Leu (c.1653C>G) is classified Uncertain significance in DNAJC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely benign (0.2168); Absent from gnomAD v4.1.

How common is DNAJC2 p.Phe551Leu (c.1653C>G) in the general population?

DNAJC2 p.Phe551Leu (c.1653C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJC2 p.Phe551Leu (c.1653C>G)?

AlphaMissense predicts likely benign (score 0.2168) — an in-silico prediction, not a clinical call.

DNAJC2 p.Phe551Leu

c.1653C>G · rs2484910231 · VCV2299740

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2168 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2168	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -4.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.017, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 7,271 bp · p 0.069 · regional, not allelic
Overall
CADD	10.22	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: DNAJC2
Protein: p.Phe551Leu
Coding: c.1653C>G
MANE Select: NM_014377
dbSNP: rs2484910231
Type: single nucleotide variant
Location: chr7:103313085 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.51 · 2 PDB
Residue 551: the sant 2 domain

Full DNAJC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC2 c.331+1G>A Uncertain significance ★ same type
DNAJC2 p.Ala308Thr Uncertain significance ★ ⚠ same type
DNAJC2 p.Ala436Gly Uncertain significance ★ ⚠ same type
DNAJC2 p.Ala48Thr Uncertain significance ★ ⚠ same type
DNAJC2 p.Ala616Thr Uncertain significance ★ ⚠ same type
DNAJC2 p.Arg105Gly Uncertain significance ★ ⚠ same type
DNAJC2 p.Arg303Gln Uncertain significance ★ ⚠ same type
DNAJC2 p.Arg321Gln 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/dnajc2-p-phe551leu (accessed [today's date]).

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