Is MTAP p.Glu84Asp (c.252G>C) pathogenic?

MTAP p.Glu84Asp (c.252G>C) is classified Uncertain significance in MTAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-21). AlphaMissense: ambiguous (0.5425); Very rare (popmax 0.0011%, sas).

How common is MTAP p.Glu84Asp (c.252G>C) in the general population?

MTAP p.Glu84Asp (c.252G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about MTAP p.Glu84Asp (c.252G>C)?

AlphaMissense predicts ambiguous (score 0.5425) — an in-silico prediction, not a clinical call.

MTAP p.Glu84Asp

c.252G>C · rs1824530237 · VCV2115224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5425 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.5425	ambiguous
REVEL	0.544	indeterminate
SaProt	LLR -10.10	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 59 kb · p 0.71 · regional, not allelic
Overall
CADD	19.71	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 0.0011% South Asian · 1/91,032 alleles

Overall 6.2e-05% 1/1,613,966 alleles · very rare exomes 1/1,461,786 · genomes 0/152,180 · joint denominator

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.Glu84Asp
Coding: c.252G>C
MANE Select: NM_002451
dbSNP: rs1824530237
Type: single nucleotide variant
Location: chr9:21818107 (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

Similar variants

MTAP c.*1453C>T Uncertain significance ★★ same type
MTAP p.Gln75Arg Uncertain significance ★★ ⚠ same type
MTAP c.120+279C>T Benign ★★ same type
MTAP c.121-10T>C Benign ★★ same type
MTAP c.121-140G>A Benign ★★ same type
MTAP c.121-185A>G Benign ★★ same type
MTAP c.121-67A>G Benign ★★ same type
MTAP c.121-76T>C Benign ★★ 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/mtap-p-glu84asp (accessed [today's date]).

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