Is JAGN1 p.Pro7= (c.21G>C) pathogenic?

JAGN1 p.Pro7= (c.21G>C) is classified Benign/Likely benign in JAGN1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-30). Common (popmax 5.25%, sas) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive severe congenital neutropenia due to JAGN1 deficiency.

JAGN1 p.Pro7=

Q: What condition is associated with JAGN1 p.Pro7= (c.21G>C)?

JAGN1 p.Pro7= (c.21G>C) is associated with autosomal recessive severe congenital neutropenia due to JAGN1 deficiency (ClinVar).

Q: How common is JAGN1 p.Pro7= (c.21G>C) in the general population?

JAGN1 p.Pro7= (c.21G>C) is common (popmax 5.25%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Severe congenital neutropenia due to JAGN1 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.21G>C · rs138937423 · VCV475245

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 5.25%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

autosomal recessive severe congenital neutropenia due to JAGN1 deficiency

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 0.23	GERP -1.9, phastCons 0.92
Overall
CADD	12.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.25% South Asian · 4,721/89,964 alleles

Filtering AF 5.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.07%

Overall 0.425% 6,847/1,609,170 alleles · common exomes 6,117/1,456,816 · genomes 730/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	5.25%	19
Admixed American	1.42%	71
Remaining individualsnot grpmax-eligible	0.62%	161
Finnishnot grpmax-eligible	0.594%	168
East Asian	0.298%	336
Middle Eastern	0.165%	604
African / African-American	0.048%	2,083
European (non-Finnish)	0.0293%	3,416
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,396

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: JAGN1
Protein: p.Pro7=
Coding: c.21G>C
MANE Select: NM_032492
dbSNP: rs138937423
Type: single nucleotide variant
Location: chr3:9890743 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.43 · 1 PDB

Full JAGN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive severe congenital neutropenia due to JAGN1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe congenital neutropenia due to JAGN1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

JAGN1 p.Ala24Val Uncertain significance ★★ ⚠ same condition
JAGN1 p.Arg131His Uncertain significance ★★ ⚠ same condition
JAGN1 p.Arg22Cys Uncertain significance ★★ ⚠ same condition
JAGN1 p.Arg4Pro Uncertain significance ★★ ⚠ same condition
JAGN1 p.Arg94Gly Uncertain significance ★★ ⚠ same condition
JAGN1 p.Asp16Tyr Uncertain significance ★★ ⚠ same condition
JAGN1 p.Ile105Val Uncertain significance ★★ ⚠ same condition
JAGN1 p.Ile112Val Uncertain significance ★★ ⚠ same condition

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/jagn1-p-pro7 (accessed [today's date]).

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