Is MAPKBP1 p.Gln751Pro (c.2252A>C) pathogenic?

MAPKBP1 p.Gln751Pro (c.2252A>C) is classified Uncertain significance in MAPKBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-09). AlphaMissense: likely benign (0.0679); Ultra-rare (popmax 0.0307%, afr); Associated with Inborn genetic diseases.

What condition is associated with MAPKBP1 p.Gln751Pro (c.2252A>C)?

MAPKBP1 p.Gln751Pro (c.2252A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MAPKBP1 p.Gln751Pro (c.2252A>C) in the general population?

MAPKBP1 p.Gln751Pro (c.2252A>C) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about MAPKBP1 p.Gln751Pro (c.2252A>C)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

MAPKBP1 p.Gln751Pro

c.2252A>C · rs907742706 · VCV2356511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -4.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 708 bp · p 1.2e-06 · regional, not allelic
Overall
CADD	19.45	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q757P vs ClinVar Q751P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,944 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00161% 26/1,614,078 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,258
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	60,000

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: MAPKBP1
Protein: p.Gln751Pro
Coding: c.2252A>C
MANE Select: NM_014994
dbSNP: rs907742706
Type: single nucleotide variant
Location: chr15:41818918 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.84 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.82
Residue 757 UniProt numbering: the 'disordered' region

Full MAPKBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAPKBP1 p.Ala1126Pro Uncertain significance ★★ ⚠ same condition
MAPKBP1 p.Ala1407Thr Uncertain significance ★★ ⚠ same condition
MAPKBP1 p.Ala1427Ser Uncertain significance ★★ ⚠ same condition
MAPKBP1 p.Ala146Thr Uncertain significance ★★ ⚠ same condition
MAPKBP1 p.Arg1314Trp Uncertain significance ★★ ⚠ same condition
MAPKBP1 p.Arg1337Ser Uncertain significance ★★ ⚠ same condition
MAPKBP1 p.Arg1425Cys Uncertain significance ★★ ⚠ same condition
MAPKBP1 p.Arg1506His Uncertain significance ★★ ⚠ 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/mapkbp1-p-gln751pro (accessed [today's date]).

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