Is MAG p.Pro66Ala (c.196C>G) pathogenic?

MAG p.Pro66Ala (c.196C>G) is classified Uncertain significance in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). AlphaMissense: likely pathogenic (0.8634); Ultra-rare (popmax 0.0428%, sas); Associated with Inborn genetic diseases.

What condition is associated with MAG p.Pro66Ala (c.196C>G)?

MAG p.Pro66Ala (c.196C>G) is associated with Inborn genetic diseases (ClinVar).

How common is MAG p.Pro66Ala (c.196C>G) in the general population?

MAG p.Pro66Ala (c.196C>G) is ultra-rare (popmax 0.0428%, sas) (gnomAD).

What do computational predictors say about MAG p.Pro66Ala (c.196C>G)?

AlphaMissense predicts likely pathogenic (score 0.8634) — an in-silico prediction, not a clinical call.

MAG p.Pro66Ala

c.196C>G · rs201532201 · VCV3122044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8634 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0428%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8634	likely pathogenic
REVEL	0.252	benign-leaning
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 18 kb · p 0.052 · regional, not allelic
Overall
CADD	28.3	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 0.0428% South Asian · 39/91,082 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.00254% 41/1,613,978 alleles · ultra-rare exomes 39/1,461,724 · genomes 2/152,254 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0428%	2,335
Remaining individualsnot grpmax-eligible	0.0032%	31,253

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: MAG
Protein: p.Pro66Ala
Coding: c.196C>G
MANE Select: NM_002361
dbSNP: rs201532201
Type: single nucleotide variant
Location: chr19:35295762 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.53
Residue 66: the 'interaction with rtn4r and rtn4rl2' region; a binding site; the ig-like v-type domain

Full MAG 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

MAG p.Ala490Thr Uncertain significance ★★ ⚠ same condition
MAG p.Arg316Leu Uncertain significance ★★ ⚠ same condition
MAG p.Arg465His Uncertain significance ★★ ⚠ same condition
MAG p.Arg563Cys Uncertain significance ★★ ⚠ same condition
MAG p.Arg576His Uncertain significance ★★ ⚠ same condition
MAG p.Arg587Gln Uncertain significance ★★ ⚠ same condition
MAG p.Asn106Lys Uncertain significance ★★ ⚠ same condition
MAG p.Asn62Ser 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/mag-p-pro66ala (accessed [today's date]).

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