Is MOGS p.His617Gln (c.1851T>A) pathogenic?

MOGS p.His617Gln (c.1851T>A) is classified Conflicting classifications of pathogenicity in MOGS (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.0801); Ultra-rare (popmax 0.0542%, nfe); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.His617Gln (c.1851T>A)?

MOGS p.His617Gln (c.1851T>A) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.His617Gln (c.1851T>A) in the general population?

MOGS p.His617Gln (c.1851T>A) is ultra-rare (popmax 0.0542%, nfe) (gnomAD).

How is MOGS-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MOGS p.His617Gln (c.1851T>A)?

AlphaMissense predicts likely benign (score 0.0801) — an in-silico prediction, not a clinical call.

MOGS p.His617Gln

c.1851T>A · rs199939051 · VCV337106

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0801 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0542%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MOGS-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0801	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -3.97	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 0.69	GERP -3.4, phastCons 0.069
Regional constraint	o/e 0.69	unconstrained · MANE · 608 bp · p 6e-07 · regional, not allelic
Overall
CADD	5.444	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 0.0542% European (non-Finnish) · 639/1,180,018 alleles

Filtering AF 0.0507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0492%

Overall 0.0689% 1,112/1,614,002 alleles · ultra-rare exomes 1,001/1,461,834 · genomes 111/152,168 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.648%	154
Remaining individualsnot grpmax-eligible	0.072%	1,388
European (non-Finnish)grpmax	0.0542%	1,847
Admixed American	0.01%	10,001
African / African-American	0.00934%	10,703

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His617Gln
Coding: c.1851T>A
MANE Select: NM_006302
dbSNP: rs199939051
Type: single nucleotide variant
Location: chr2:74461938 (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

MOGS-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MOGS-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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
MOGS p.Ala510Thr 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-his617gln (accessed [today's date]).

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