Is MAPKBP1 p.Pro77= (c.231C>A) pathogenic?

MAPKBP1 p.Pro77= (c.231C>A) is classified Likely benign in MAPKBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). Ultra-rare (popmax 0.0264%, sas).

How common is MAPKBP1 p.Pro77= (c.231C>A) in the general population?

MAPKBP1 p.Pro77= (c.231C>A) is ultra-rare (popmax 0.0264%, sas) (gnomAD).

MAPKBP1 p.Pro77=

c.231C>A · VCV4749570

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0264%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.359	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP 0.37, phastCons 0.92
Overall
CADD	10.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0264% South Asian · 24/91,080 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0154%

Overall 0.00155% 25/1,614,102 alleles · ultra-rare exomes 24/1,461,888 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0264%	3,795
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Pro77=
Coding: c.231C>A
MANE Select: NM_014994
Type: single nucleotide variant
Location: chr15:41810907 (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-pro77 (accessed [today's date]).

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