Is MAPKBP1 p.Pro620Ser (c.1858C>T) pathogenic?

MAPKBP1 p.Pro620Ser (c.1858C>T) is classified Uncertain significance in MAPKBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: ambiguous (0.4001); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with MAPKBP1 p.Pro620Ser (c.1858C>T)?

MAPKBP1 p.Pro620Ser (c.1858C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MAPKBP1 p.Pro620Ser (c.1858C>T) in the general population?

MAPKBP1 p.Pro620Ser (c.1858C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about MAPKBP1 p.Pro620Ser (c.1858C>T)?

AlphaMissense predicts ambiguous (score 0.4001) — an in-silico prediction, not a clinical call.

MAPKBP1 p.Pro620Ser

c.1858C>T · VCV3543239

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4001	ambiguous
REVEL	0.3	indeterminate
SaProt	LLR -5.25	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.2, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 5,625 bp · p 4.8e-14 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P626S vs ClinVar P620S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,020 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,176 alleles · very rare exomes 2/1,461,872 · genomes 0/152,304 · 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: MAPKBP1
Protein: p.Pro620Ser
Coding: c.1858C>T
MANE Select: NM_014994
Type: single nucleotide variant
Location: chr15:41817689 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.84 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.82

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-pro620ser (accessed [today's date]).

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