Is GEMIN4 p.Arg773= (c.2319G>A) pathogenic?

GEMIN4 p.Arg773= (c.2319G>A) is classified Likely benign in GEMIN4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-17). Very rare (popmax 8.5e-05%, nfe); Associated with GEMIN4-related disorder.

What condition is associated with GEMIN4 p.Arg773= (c.2319G>A)?

GEMIN4 p.Arg773= (c.2319G>A) is associated with GEMIN4-related disorder (ClinVar).

How common is GEMIN4 p.Arg773= (c.2319G>A) in the general population?

GEMIN4 p.Arg773= (c.2319G>A) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

GEMIN4 p.Arg773=

c.2319G>A · rs2544536911 · VCV3040236

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Conditions

GEMIN4-related disorder

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 -0.16	GERP -2.7, phastCons 0.67
Overall
CADD	0.537	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,712 alleles

Overall 6.22e-05% 1/1,606,658 alleles · very rare exomes 1/1,454,348 · genomes 0/152,310 · joint denominator

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: GEMIN4
Protein: p.Arg773=
Coding: c.2319G>A
MANE Select: NM_015721
dbSNP: rs2544536911
Type: single nucleotide variant
Location: chr17:745724 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.54

Full GEMIN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GEMIN4-related disorder

Similar variants

GEMIN4 p.Glu146Lys Uncertain significance ★ ⚠ same condition
GEMIN4 p.Trp92Cys Uncertain significance ★ ⚠ same condition
GEMIN4 p.Glu844= Likely benign same condition
GEMIN4 p.Gly18= Likely benign same condition
GEMIN4 p.Gly812= Likely benign same condition
GEMIN4 p.Gly945= Likely benign same condition
GEMIN4 p.Ile1042= Benign same condition
GEMIN4 p.Asp350fs Likely pathogenic ★ 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/gemin4-p-arg773 (accessed [today's date]).

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