Is MAPKBP1 p.Ser407= (c.1221C>T) pathogenic?

MAPKBP1 p.Ser407= (c.1221C>T) is classified Likely benign in MAPKBP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-11-22). Ultra-rare (popmax 0.0383%, amr).

How common is MAPKBP1 p.Ser407= (c.1221C>T) in the general population?

MAPKBP1 p.Ser407= (c.1221C>T) is ultra-rare (popmax 0.0383%, amr) (gnomAD).

MAPKBP1 p.Ser407=

c.1221C>T · rs766915233 · VCV1901080

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP -4.6, phastCons 0.99
Overall
CADD	10.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0383% Admixed American · 23/60,014 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00142% 23/1,614,104 alleles · ultra-rare exomes 20/1,461,894 · genomes 3/152,210 · 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.Ser407=
Coding: c.1221C>T
MANE Select: NM_014994
dbSNP: rs766915233
Type: single nucleotide variant
Location: chr15:41815309 (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

Similar variants

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
MAPKBP1 p.Arg1314Trp Uncertain significance ★★ ⚠ same type
MAPKBP1 p.Arg1337Ser 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-ser407 (accessed [today's date]).

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