Is MAFB p.Arg38= (c.114C>A) pathogenic?

MAFB p.Arg38= (c.114C>A) is classified Likely benign in MAFB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-01). Ultra-rare (popmax 0.0285%, sas); Associated with MAFB-related disorder.

What condition is associated with MAFB p.Arg38= (c.114C>A)?

MAFB p.Arg38= (c.114C>A) is associated with MAFB-related disorder (ClinVar).

How common is MAFB p.Arg38= (c.114C>A) in the general population?

MAFB p.Arg38= (c.114C>A) is ultra-rare (popmax 0.0285%, sas) (gnomAD).

MAFB p.Arg38=

c.114C>A · rs764292811 · VCV3046482

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, sas)

Conditions

MAFB-related disorder

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 0.16	GERP -4.8, phastCons 0.4
Overall
CADD	8.554	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0285% South Asian · 26/91,088 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00198% 32/1,613,784 alleles · ultra-rare exomes 30/1,461,522 · genomes 2/152,262 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0285%	3,503
Remaining individualsnot grpmax-eligible	0.0016%	62,474
European (non-Finnish)	0.000424%	235,983

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: MAFB
Protein: p.Arg38=
Coding: c.114C>A
MANE Select: NM_005461
dbSNP: rs764292811
Type: single nucleotide variant
Location: chr20:40688737 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.87
Residue 38: the 'disordered' region

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

Disease context

MAFB-related disorder

Similar variants

MAFB p.Arg38Gly Uncertain significance ★ ⚠ same residue
MAFB p.Pro63Leu Pathogenic ★★ same condition
MAFB p.Ser54Leu Pathogenic ★★ ⚠ same condition
MAFB p.Ser69Leu Pathogenic/Likely pathogenic ★★ same condition
MAFB p.Arg249Gly Likely pathogenic ★ same condition
MAFB p.Ser65Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
MAFB p.Glu4Ala Uncertain significance same condition
MAFB p.Gly113Arg 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-arg38 (accessed [today's date]).

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