Is MOGS p.Ala780Thr (c.2338G>A) pathogenic?

MOGS p.Ala780Thr (c.2338G>A) is classified Uncertain significance in MOGS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-07). AlphaMissense: likely benign (0.2414); Ultra-rare (popmax 0.0133%, afr); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Ala780Thr (c.2338G>A)?

MOGS p.Ala780Thr (c.2338G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MOGS p.Ala780Thr (c.2338G>A) in the general population?

MOGS p.Ala780Thr (c.2338G>A) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about MOGS p.Ala780Thr (c.2338G>A)?

AlphaMissense predicts likely benign (score 0.2414) — an in-silico prediction, not a clinical call.

MOGS p.Ala780Thr

c.2338G>A · rs764633080 · VCV2577770

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2414 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2414	likely benign
REVEL	0.311	indeterminate
SaProt	LLR -11.86	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
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	26.0	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 0.0133% African / African-American · 10/74,950 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000805% 13/1,614,098 alleles · ultra-rare exomes 5/1,461,838 · genomes 8/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,495
Admixed American	0.00333%	30,006
South Asian	0.0011%	91,092

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.Ala780Thr
Coding: c.2338G>A
MANE Select: NM_006302
dbSNP: rs764633080
Type: single nucleotide variant
Location: chr2:74461451 (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.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.Arg241His Uncertain significance ★★ ⚠ same condition
MOGS p.Arg280Pro Uncertain significance ★★ ⚠ same condition
MOGS p.Arg33Leu Uncertain significance ★★ ⚠ same condition
MOGS p.Arg371His 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-ala780thr (accessed [today's date]).

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