Is MAFB p.Pro63Ser (c.187C>T) pathogenic?

MAFB p.Pro63Ser (c.187C>T) is classified Pathogenic in MAFB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-31). AlphaMissense: likely pathogenic (0.9879); Absent from gnomAD v4.1.

How common is MAFB p.Pro63Ser (c.187C>T) in the general population?

MAFB p.Pro63Ser (c.187C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAFB p.Pro63Ser (c.187C>T)?

AlphaMissense predicts likely pathogenic (score 0.9879) — an in-silico prediction, not a clinical call.

MAFB p.Pro63Ser

c.187C>T · rs2515463636 · VCV2031466

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9879 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9879	likely pathogenic ✓ concordant with ClinVar
REVEL	0.765	pathogenic-leaning
SaProt	LLR -11.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 710 bp · p 0.00051 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: MAFB
Protein: p.Pro63Ser
Coding: c.187C>T
MANE Select: NM_005461
dbSNP: rs2515463636
Type: single nucleotide variant
Location: chr20:40688664 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.87
Residue 63: a UniProt-annotated variant site (in mcto); the 'disordered' region

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

Similar variants

MAFB p.Pro63Leu Pathogenic ★★ same residue
MAFB p.Pro63= Conflicting classifications of pathogenicity ★ same residue
MAFB p.Pro59Leu Pathogenic/Likely pathogenic ★★ same type
MAFB p.Ser54Leu Pathogenic ★★ ⚠ same type
MAFB p.Ser69Leu Pathogenic/Likely pathogenic ★★ same type
MAFB p.Ser70Leu Pathogenic/Likely pathogenic ★★ same type
MAFB p.Thr62Ala Pathogenic ★★ same type
MAFB c.-77C>G 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/mafb-p-pro63ser (accessed [today's date]).

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