Is ORC1 p.Glu809= (c.2427G>A) pathogenic?

ORC1 p.Glu809= (c.2427G>A) is classified Benign in ORC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-14). Low-frequency (popmax 4.18%, sas); Associated with Meier-Gorlin syndrome 1.

What condition is associated with ORC1 p.Glu809= (c.2427G>A)?

ORC1 p.Glu809= (c.2427G>A) is associated with Meier-Gorlin syndrome 1 (ClinVar).

How common is ORC1 p.Glu809= (c.2427G>A) in the general population?

ORC1 p.Glu809= (c.2427G>A) is low-frequency (popmax 4.18%, sas) (gnomAD).

ORC1 p.Glu809=

c.2427G>A · rs77077945 · VCV129859

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.18%, sas)

Conditions

Meier-Gorlin syndrome 1

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 0.52	GERP 1.4, phastCons 1
Overall
CADD	2.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.18% South Asian · 3,805/91,084 alleles

Filtering AF 4.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.02%

Overall 0.589% 9,511/1,614,146 alleles · low-frequency exomes 8,901/1,461,828 · genomes 610/152,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	4.18%	24
East Asian	3.29%	30
Remaining individualsnot grpmax-eligible	0.653%	153
European (non-Finnish)	0.307%	326
Middle Eastern	0.28%	357
Admixed American	0.122%	822
Ashkenazi Jewishnot grpmax-eligible	0.118%	846
African / African-American	0.072%	1,390
Finnishnot grpmax-eligible	0.0359%	2,783

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: ORC1
Protein: p.Glu809=
Coding: c.2427G>A
MANE Select: NM_004153
dbSNP: rs77077945
Type: single nucleotide variant
Location: chr1:52373340 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.80 · 14 PDB
Residue 809: the 'necessary and sufficient for orc complex assembly' region; an α-helix

Full ORC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Meier-Gorlin syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ORC1 p.Arg105Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ORC1 p.Arg105Trp Likely pathogenic ★★ ⚠ same condition
ORC1 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same condition
ORC1 p.Arg720Gln Likely pathogenic ★★ same condition
ORC1 p.Ala174Val Uncertain significance ★★ ⚠ same condition
ORC1 p.Ala597Thr Uncertain significance ★★ ⚠ same condition
ORC1 p.Ala857Val Uncertain significance ★★ ⚠ same condition
ORC1 p.Ala97Ser 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/orc1-p-glu809 (accessed [today's date]).

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