Is MTAP p.Pro143Leu (c.428C>T) pathogenic?

MTAP p.Pro143Leu (c.428C>T) is classified Uncertain significance in MTAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely pathogenic (0.7915); Very rare (popmax 0.00267%, afr).

How common is MTAP p.Pro143Leu (c.428C>T) in the general population?

MTAP p.Pro143Leu (c.428C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about MTAP p.Pro143Leu (c.428C>T)?

AlphaMissense predicts likely pathogenic (score 0.7915) — an in-silico prediction, not a clinical call.

MTAP p.Pro143Leu

c.428C>T · rs764360382 · VCV2225526

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7915 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7915	likely pathogenic
REVEL	0.759	pathogenic-leaning
SaProt	LLR -17.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 59 kb · p 0.71 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,862 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00031% 5/1,613,850 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,431
European (non-Finnish)	0.000254%	393,311

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.Pro143Leu
Coding: c.428C>T
MANE Select: NM_002451
dbSNP: rs764360382
Type: single nucleotide variant
Location: chr9:21837988 (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-pro143leu (accessed [today's date]).

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