Is MAPKBP1 p.Pro775Ala (c.2323C>G) pathogenic?

MAPKBP1 p.Pro775Ala (c.2323C>G) is classified Uncertain significance in MAPKBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). AlphaMissense: likely benign (0.0671); Absent from gnomAD v4.1.

How common is MAPKBP1 p.Pro775Ala (c.2323C>G) in the general population?

MAPKBP1 p.Pro775Ala (c.2323C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPKBP1 p.Pro775Ala (c.2323C>G)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

MAPKBP1 p.Pro775Ala

c.2323C>G · VCV3380260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	acceptor loss, 16 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 6,487 bp · p 0.72 · regional, not allelic
Overall
CADD	19.59	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 P781A vs ClinVar P775A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAPKBP1
Protein: p.Pro775Ala
Coding: c.2323C>G
MANE Select: NM_014994
Type: single nucleotide variant
Location: chr15:41819277 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.84 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.82
Residue 781 UniProt numbering: the 'disordered' region

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

Similar variants

MAPKBP1 p.Pro775Leu Uncertain significance ★ ⚠ same residue
MAPKBP1 p.Pro775= Likely benign ★ same residue
MAPKBP1 c.1711+5G>A Uncertain significance ★★ same type
MAPKBP1 p.Ala1126Pro Uncertain significance ★★ ⚠ same type
MAPKBP1 p.Ala1407Thr Uncertain significance ★★ ⚠ same type
MAPKBP1 p.Ala1427Ser Uncertain significance ★★ ⚠ same type
MAPKBP1 p.Ala146Thr Uncertain significance ★★ ⚠ same type
MAPKBP1 p.Arg1102Cys Uncertain significance ★★ ⚠ 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/mapkbp1-p-pro775ala (accessed [today's date]).

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