Is DNAJC7 p.Pro193= (c.579A>G) pathogenic?

DNAJC7 p.Pro193= (c.579A>G) is classified Benign in DNAJC7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-04). Common (popmax 20.2%, afr) — too common for a highly-penetrant pathogenic allele.

DNAJC7 p.Pro193=

Q: How common is DNAJC7 p.Pro193= (c.579A>G) in the general population?

DNAJC7 p.Pro193= (c.579A>G) is common (popmax 20.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.579A>G · rs1127182 · VCV1261815

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 20.2%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.68	GERP -0.25, phastCons 1
Overall
CADD	9.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.2% African / African-American · 15,149/74,908 alleles

Filtering AF 20% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.8%

Overall 7.61% 122,480/1,609,772 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	20.2%	5
East Asian	13.6%	7
South Asian	11.4%	9
Remaining individualsnot grpmax-eligible	8.08%	12
Middle Eastern	7.96%	13
Finnishnot grpmax-eligible	7.61%	13
Ashkenazi Jewishnot grpmax-eligible	7.33%	14
European (non-Finnish)	6.41%	16
Amishnot grpmax-eligible	5.48%	18
Admixed American	4.74%	21

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: DNAJC7
Protein: p.Pro193=
Coding: c.579A>G
MANE Select: NM_003315
dbSNP: rs1127182
Type: single nucleotide variant
Location: chr17:41990284 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.83

Full DNAJC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC7 c.167-65C>A Benign ★★ same type
DNAJC7 c.406-8C>T Benign ★★ same type
DNAJC7 c.599+161G>A Benign ★★ same type
DNAJC7 p.Ala115Pro Uncertain significance ★ ⚠ same type
DNAJC7 p.Ala141Thr Uncertain significance ★ ⚠ same type
DNAJC7 p.Ala370Val Uncertain significance ★ ⚠ same type
DNAJC7 p.Ala4Val Uncertain significance ★ ⚠ same type
DNAJC7 p.Arg117His 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/dnajc7-p-pro193 (accessed [today's date]).

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