Is MTAP p.Pro256= (c.768T>G) pathogenic?

MTAP p.Pro256= (c.768T>G) is classified Benign/Likely benign in MTAP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-01). Rare (popmax 0.988%, nfe); Associated with diaphyseal medullary stenosis-bone malignancy syndrome.

What condition is associated with MTAP p.Pro256= (c.768T>G)?

MTAP p.Pro256= (c.768T>G) is associated with diaphyseal medullary stenosis-bone malignancy syndrome (ClinVar).

How common is MTAP p.Pro256= (c.768T>G) in the general population?

MTAP p.Pro256= (c.768T>G) is rare (popmax 0.988%, nfe) (gnomAD).

MTAP p.Pro256=

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.768T>G · rs62556500 · VCV366249

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.988%, nfe)

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 0.029	GERP -2.4, phastCons 0.95
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.988% European (non-Finnish) · 11,653/1,179,650 alleles

Filtering AF 0.973% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.967%

Overall 0.779% 12,569/1,613,362 alleles · rare exomes 11,817/1,461,098 · genomes 752/152,264 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.988%	101
Amishnot grpmax-eligible	0.768%	130
Finnishnot grpmax-eligible	0.469%	213
Remaining individualsnot grpmax-eligible	0.461%	217
Middle Eastern	0.198%	505
Admixed American	0.134%	749
South Asian	0.131%	764
African / African-American	0.127%	790
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,973

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.Pro256=
Coding: c.768T>G
MANE Select: NM_002451
dbSNP: rs62556500
Type: single nucleotide variant
Location: chr9:21859380 (GRCh38)
Gene constraint: LOEUF 1.489 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 92.99 · 18 PDB
Residue 256: an α-helix

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-pro256 (accessed [today's date]).

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