Is MOGS p.Arg820His (c.2459G>A) pathogenic?

MOGS p.Arg820His (c.2459G>A) is classified Uncertain significance in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.0703); Ultra-rare (popmax 0.0223%, eas); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Arg820His (c.2459G>A)?

MOGS p.Arg820His (c.2459G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MOGS p.Arg820His (c.2459G>A) in the general population?

MOGS p.Arg820His (c.2459G>A) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about MOGS p.Arg820His (c.2459G>A)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

MOGS p.Arg820His

c.2459G>A · VCV4109499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -3.15	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 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 601 bp · p 0.59 · regional, not allelic
Overall
CADD	23.8	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 0.0223% East Asian · 10/44,902 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00118% 19/1,613,974 alleles · ultra-rare exomes 16/1,461,716 · genomes 3/152,258 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,490
South Asian	0.00329%	30,365
African / African-American	0.00133%	74,950
European (non-Finnish)	0.000424%	236,009

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.Arg820His
Coding: c.2459G>A
MANE Select: NM_006302
Type: single nucleotide variant
Location: chr2:74461330 (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

Similar variants

MOGS p.Arg820Cys Uncertain significance ★ ⚠ same residue
MOGS p.Ala292Asp Uncertain significance ★★ ⚠ same condition
MOGS p.Ala292Pro Uncertain significance ★★ ⚠ same condition
MOGS p.Ala41Val Uncertain significance ★★ ⚠ same condition
MOGS p.Ala688Thr Uncertain significance ★★ ⚠ same condition
MOGS p.Ala780Thr Uncertain significance ★★ ⚠ same condition
MOGS p.Arg241His Uncertain significance ★★ ⚠ same condition
MOGS p.Arg280Pro 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-arg820his (accessed [today's date]).

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