Is MOGS p.Val424= (c.1272G>A) pathogenic?

MOGS p.Val424= (c.1272G>A) is classified Likely benign in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-10). Very rare (popmax 0.00221%, nfe); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Val424= (c.1272G>A)?

MOGS p.Val424= (c.1272G>A) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Val424= (c.1272G>A) in the general population?

MOGS p.Val424= (c.1272G>A) is very rare (popmax 0.00221%, nfe) (gnomAD).

How is MOGS-CDG inherited?

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

MOGS p.Val424=

c.1272G>A · rs765917880 · VCV1618384

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

Conditions

MOGS-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.30 · evaluated, not missing
Pangolin	Δ0.25	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -0.42	GERP -2.1, phastCons 0.002
Overall
CADD	3.565	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% European (non-Finnish) · 26/1,175,752 alleles

Filtering AF 0.00154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00131%

Overall 0.00174% 28/1,607,570 alleles · very rare exomes 28/1,455,248 · genomes 0/152,322 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00221%	45,221
Remaining individualsnot grpmax-eligible	0.00161%	62,108
African / African-American	0.00134%	74,796

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.Val424=
Coding: c.1272G>A
MANE Select: NM_006302
dbSNP: rs765917880
Type: single nucleotide variant
Location: chr2:74462517 (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-val424 (accessed [today's date]).

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