Is MGMT p.Arg9= (c.27C>T) pathogenic?

MGMT p.Arg9= (c.27C>T) is classified Uncertain significance in MGMT (ClinVar, Single submitter, 1 submitter; last evaluated 2016-02-25). Very rare (popmax 0.00549%, sas).

How common is MGMT p.Arg9= (c.27C>T) in the general population?

MGMT p.Arg9= (c.27C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

MGMT p.Arg9=

c.27C>T · rs748231906 · VCV286330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.5	GERP 1.9, phastCons 0.027
Overall
CADD	6.553	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,054 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000558% 9/1,614,028 alleles · very rare exomes 9/1,461,762 · genomes 0/152,266 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,211
African / African-American	0.004%	25,003
European (non-Finnish)	8.47e-05%	1,180,016

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: MGMT
Protein: p.Arg9=
Coding: c.27C>T
MANE Select: NM_002412
dbSNP: rs748231906
Type: single nucleotide variant
Location: chr10:129536279 (GRCh38)
Gene constraint: LOEUF 1.413 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.86 · 23 PDB
Residue 9: a β-strand

Full MGMT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MGMT p.Arg9Leu Uncertain significance ★ ⚠ same residue
MGMT p.Glu30Lys Likely benign ★★ same type
MGMT p.Lys178Arg Benign ★★ same type
MGMT c.-54C>G Uncertain significance ★ same type
MGMT c.-60G>T Uncertain significance ★ same type
MGMT p.Ala126Gly Uncertain significance ★ ⚠ same type
MGMT p.Ala197Thr Uncertain significance ★ ⚠ same type
MGMT p.Ala68Thr Uncertain significance ★ ⚠ same type

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/mgmt-p-arg9 (accessed [today's date]).

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