Is MOGS p.Arg506Gln (c.1517G>A) pathogenic?

MOGS p.Arg506Gln (c.1517G>A) is classified Conflicting classifications of pathogenicity in MOGS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-12). AlphaMissense: likely benign (0.0838); Rare (popmax 0.232%, eas); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Arg506Gln (c.1517G>A)?

MOGS p.Arg506Gln (c.1517G>A) is associated with Inborn genetic diseases, MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Arg506Gln (c.1517G>A) in the general population?

MOGS p.Arg506Gln (c.1517G>A) is rare (popmax 0.232%, eas) (gnomAD).

What do computational predictors say about MOGS p.Arg506Gln (c.1517G>A)?

AlphaMissense predicts likely benign (score 0.0838) — an in-silico prediction, not a clinical call.

MOGS p.Arg506Gln

c.1517G>A · rs757364620 · VCV1368165

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0838 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.232%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0838	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -8.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.62	GERP -0.75, phastCons 0.19
Regional constraint	o/e 0.69	unconstrained · MANE · 608 bp · p 6e-07 · regional, not allelic
Overall
CADD	14.39	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 0.232% East Asian · 104/44,892 alleles

Filtering AF 0.196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.182%

Overall 0.00973% 157/1,613,750 alleles · rare exomes 155/1,461,632 · genomes 2/152,118 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.232%	432
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.00407%	24,584
African / African-American	0.00134%	74,884

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.Arg506Gln
Coding: c.1517G>A
MANE Select: NM_006302
dbSNP: rs757364620
Type: single nucleotide variant
Location: chr2:74462272 (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.Arg506Ter Pathogenic ★ same residue
MOGS p.Arg506= Likely benign ★ 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

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-arg506gln (accessed [today's date]).

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