Is MOGS p.Arg609His (c.1826G>A) pathogenic?

MOGS p.Arg609His (c.1826G>A) is classified Uncertain significance in MOGS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-21). AlphaMissense: likely benign (0.1065); Ultra-rare (popmax 0.0376%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Arg609His (c.1826G>A)?

MOGS p.Arg609His (c.1826G>A) is associated with Inborn genetic diseases, MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Arg609His (c.1826G>A) in the general population?

MOGS p.Arg609His (c.1826G>A) is ultra-rare (popmax 0.0376%, nfe) (gnomAD).

What do computational predictors say about MOGS p.Arg609His (c.1826G>A)?

AlphaMissense predicts likely benign (score 0.1065) — an in-silico prediction, not a clinical call.

MOGS p.Arg609His

c.1826G>A · rs377287243 · VCV626140

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1065 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0376%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1065	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.5, phastCons 0.83
Regional constraint	o/e 0.69	unconstrained · MANE · 608 bp · p 6e-07 · regional, not allelic
Overall
CADD	25.2	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 0.0376% European (non-Finnish) · 444/1,180,028 alleles

Filtering AF 0.0347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0336%

Overall 0.0291% 470/1,614,052 alleles · ultra-rare exomes 445/1,461,856 · genomes 25/152,196 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0376%	2,658
Remaining individualsnot grpmax-eligible	0.0176%	5,680
Middle Eastern	0.0164%	6,084
African / African-American	0.012%	8,326
South Asian	0.00329%	30,362
East Asian	0.00223%	44,886
Admixed American	0.00167%	60,008

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: MOGS
Protein: p.Arg609His
Coding: c.1826G>A
MANE Select: NM_006302
dbSNP: rs377287243
Type: single nucleotide variant
Location: chr2:74461963 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.42

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: MOGS-congenital disorder of glycosylation

Similar variants

MOGS p.Arg609Cys Uncertain significance ★ ⚠ same residue
MOGS p.Arg495Ter Pathogenic/Likely pathogenic ★★ same condition
MOGS p.Gln124Ter Pathogenic ★★ same condition
MOGS p.Gln505Ter Pathogenic/Likely pathogenic ★★ same condition
MOGS p.Ala22Glu Uncertain significance ★★ ⚠ same condition
MOGS p.Ala292Asp Uncertain significance ★★ ⚠ same condition
MOGS p.Ala292Pro Uncertain significance ★★ ⚠ same condition
MOGS p.Ala41Val 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/mogs-p-arg609his (accessed [today's date]).

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