Is MOGS p.Arg9His (c.26G>A) pathogenic?

MOGS p.Arg9His (c.26G>A) is classified Uncertain significance in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: ambiguous (0.3613); Very rare (popmax 0.0068%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Arg9His (c.26G>A)?

MOGS p.Arg9His (c.26G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MOGS p.Arg9His (c.26G>A) in the general population?

MOGS p.Arg9His (c.26G>A) is very rare (popmax 0.0068%, nfe) (gnomAD).

What do computational predictors say about MOGS p.Arg9His (c.26G>A)?

AlphaMissense predicts ambiguous (score 0.3613) — an in-silico prediction, not a clinical call.

MOGS p.Arg9His

c.26G>A · rs775230292 · VCV2509981

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0068%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3613	ambiguous
REVEL	0.118	moderately benign-leaning
SaProt	LLR -9.16	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,758 bp · p 0.9 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0068% European (non-Finnish) · 76/1,118,040 alleles

Filtering AF 0.00557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00508%

Overall 0.00538% 78/1,450,412 alleles · very rare exomes 73/1,298,178 · genomes 5/152,234 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0068%	14,711
Remaining individualsnot grpmax-eligible	0.00359%	27,853

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.Arg9His
Coding: c.26G>A
MANE Select: NM_006302
dbSNP: rs775230292
Type: single nucleotide variant
Location: chr2:74465222 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.42
Residue 9: the 'disordered' region

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.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
MOGS p.Arg33Leu 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-arg9his (accessed [today's date]).

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