Is MTAP p.Glu100= (c.300G>A) pathogenic?

MTAP p.Glu100= (c.300G>A) is classified Uncertain significance in MTAP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0111%, eas); Associated with diaphyseal medullary stenosis-bone malignancy syndrome.

What condition is associated with MTAP p.Glu100= (c.300G>A)?

MTAP p.Glu100= (c.300G>A) is associated with diaphyseal medullary stenosis-bone malignancy syndrome (ClinVar).

How common is MTAP p.Glu100= (c.300G>A) in the general population?

MTAP p.Glu100= (c.300G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

MTAP p.Glu100=

Q: How is Diaphyseal medullary stenosis-bone malignancy syndrome inherited?

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

c.300G>A · rs762121645 · VCV366241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Conditions

diaphyseal medullary stenosis-bone malignancy syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.81	GERP -3.6
Overall
CADD	3.212	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,864 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000434% 7/1,613,766 alleles · ultra-rare exomes 6/1,461,772 · genomes 1/151,994 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,973
South Asian	0.0011%	91,038
European (non-Finnish)	8.47e-05%	1,179,972

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: MTAP
Protein: p.Glu100=
Coding: c.300G>A
MANE Select: NM_002451
dbSNP: rs762121645
Type: single nucleotide variant
Location: chr9:21818155 (GRCh38)
Gene constraint: LOEUF 1.489 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 92.99 · 18 PDB

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

Disease context

diaphyseal medullary stenosis-bone malignancy syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Diaphyseal medullary stenosis-bone malignancy syndrome (Orphanet):

Inheritance: Autosomal dominant

Similar variants

MTAP c.*1453C>T Uncertain significance ★★ same condition
MTAP p.Gln75Arg Uncertain significance ★★ ⚠ same condition
MTAP c.121-10T>C Benign ★★ same condition
MTAP c.179+12T>A Benign/Likely benign ★★ same condition
MTAP c.*2085G>A Benign ★★ same condition
MTAP c.*2365C>T Benign ★★ same condition
MTAP c.*2522A>G Benign ★★ same condition
MTAP c.*258A>C Benign ★★ 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/mtap-p-glu100 (accessed [today's date]).

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