Is MAFB p.Pro71Ser (c.211C>T) pathogenic?

MAFB p.Pro71Ser (c.211C>T) is classified Likely pathogenic in MAFB (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-15). AlphaMissense: likely pathogenic (0.9954); Absent from gnomAD v4.1; Associated with multicentric carpo-tarsal osteolysis with or without nephropathy.

What condition is associated with MAFB p.Pro71Ser (c.211C>T)?

MAFB p.Pro71Ser (c.211C>T) is associated with multicentric carpo-tarsal osteolysis with or without nephropathy (ClinVar).

How common is MAFB p.Pro71Ser (c.211C>T) in the general population?

MAFB p.Pro71Ser (c.211C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAFB p.Pro71Ser (c.211C>T)?

AlphaMissense predicts likely pathogenic (score 0.9954) — an in-silico prediction, not a clinical call.

MAFB p.Pro71Ser

c.211C>T · rs387907007 · VCV30771

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9954 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multicentric carpo-tarsal osteolysis with or without nephropathy

Computational evidence

Protein change
AlphaMissense	0.9954	likely pathogenic ✓ concordant with ClinVar
REVEL	0.86	moderately pathogenic-leaning
SaProt	LLR -10.73	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 9.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 710 bp · p 0.00051 · regional, not allelic
Overall
CADD	32.0	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.Pro71Ser
Coding: c.211C>T
MANE Select: NM_005461
dbSNP: rs387907007
Type: single nucleotide variant
Location: chr20:40688640 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.87
Residue 71: the 'disordered' region; a UniProt-annotated variant site (in mcto)

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

Disease context

multicentric carpo-tarsal osteolysis with or without nephropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAFB p.Pro71Leu Pathogenic ★ same residue
MAFB p.Pro59Leu Pathogenic/Likely pathogenic ★★ same condition
MAFB p.Ser54Leu Pathogenic ★★ ⚠ same condition
MAFB p.Ser70Leu Pathogenic/Likely pathogenic ★★ same condition
MAFB p.Thr62Ala Pathogenic ★★ same condition
MAFB c.-77C>G Uncertain significance ★★ same condition
MAFB p.Ala110Glu Uncertain significance ★★ ⚠ same condition
MAFB p.Ala176Thr 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/mafb-p-pro71ser (accessed [today's date]).

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