Is DNAJC2 p.Pro574Ser (c.1720C>T) pathogenic?

DNAJC2 p.Pro574Ser (c.1720C>T) is classified Uncertain significance in DNAJC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.1003); Very rare (popmax 0.0011%, sas).

How common is DNAJC2 p.Pro574Ser (c.1720C>T) in the general population?

DNAJC2 p.Pro574Ser (c.1720C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DNAJC2 p.Pro574Ser (c.1720C>T)?

AlphaMissense predicts likely benign (score 0.1003) — an in-silico prediction, not a clinical call.

DNAJC2 p.Pro574Ser

c.1720C>T · VCV4013644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1003 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1003	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -8.10	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 7,271 bp · p 0.069 · regional, not allelic
Overall
CADD	23.3	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

Grpmax group 0.0011% South Asian · 1/91,068 alleles

Overall 0.000124% 2/1,613,904 alleles · very rare exomes 2/1,461,694 · genomes 0/152,210 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,068
European (non-Finnish)	8.48e-05%	1,179,922

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: DNAJC2
Protein: p.Pro574Ser
Coding: c.1720C>T
MANE Select: NM_014377
Type: single nucleotide variant
Location: chr7:103313018 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.51 · 2 PDB
Residue 574: the sant 2 domain

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

Similar variants

DNAJC2 p.Pro574Thr Uncertain significance ★ ⚠ same residue
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

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-pro574ser (accessed [today's date]).

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