Is MTAP p.Arg187= (c.561C>T) pathogenic?

MTAP p.Arg187= (c.561C>T) is classified Benign in MTAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-07-07). Common (popmax 9.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with diaphyseal medullary stenosis-bone malignancy syndrome.

What condition is associated with MTAP p.Arg187= (c.561C>T)?

MTAP p.Arg187= (c.561C>T) is associated with diaphyseal medullary stenosis-bone malignancy syndrome (ClinVar).

MTAP p.Arg187=

Q: How common is MTAP p.Arg187= (c.561C>T) in the general population?

MTAP p.Arg187= (c.561C>T) is common (popmax 9.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.561C>T · rs10965163 · VCV366244

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 9.1%, nfe) — too common for a highly-penetrant pathogenic allele

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 -2.4	GERP -3.2
Overall
CADD	7.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.1% European (non-Finnish) · 107,430/1,179,950 alleles

Filtering AF 9.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.04%

Overall 8.04% 129,776/1,614,066 alleles · common exomes 120,694/1,461,784 · genomes 9,082/152,282 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	12.6%	8
European (non-Finnish)grpmax	9.1%	11
Remaining individualsnot grpmax-eligible	7.58%	13
Middle Eastern	7.03%	14
Admixed American	6.08%	16
East Asian	4.7%	21
South Asian	4.66%	21
Finnishnot grpmax-eligible	3.55%	28
Amishnot grpmax-eligible	2.08%	48
African / African-American	1.56%	64

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg187=
Coding: c.561C>T
MANE Select: NM_002451
dbSNP: rs10965163
Type: single nucleotide variant
Location: chr9:21854741 (GRCh38)
Gene constraint: LOEUF 1.489 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 92.99 · 18 PDB
Residue 187: 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 p.Arg187Cys Uncertain significance ★ ⚠ same residue
MTAP p.Arg187His Likely benign ⚠ same residue
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

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-arg187 (accessed [today's date]).

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