Is MAFA p.Ser64Phe (c.191C>T) pathogenic?

MAFA p.Ser64Phe (c.191C>T) is classified Likely pathogenic in MAFA (ClinVar, Single submitter, 2 submitters; last evaluated 2018-10-15). AlphaMissense: likely pathogenic (0.995); No allele count reported in gnomAD v4.1 (AN 1,315,704); Associated with islet cell adenomatosis.

What condition is associated with MAFA p.Ser64Phe (c.191C>T)?

MAFA p.Ser64Phe (c.191C>T) is associated with islet cell adenomatosis (ClinVar).

How common is MAFA p.Ser64Phe (c.191C>T) in the general population?

MAFA p.Ser64Phe (c.191C>T) is no allele count reported in gnomAD v4.1 (AN 1,315,704) (gnomAD).

What do computational predictors say about MAFA p.Ser64Phe (c.191C>T)?

AlphaMissense predicts likely pathogenic (score 0.995) — an in-silico prediction, not a clinical call.

MAFA p.Ser64Phe

c.191C>T · rs1554635488 · VCV496645

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.995 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,315,704)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

islet cell adenomatosis

Computational evidence

Protein change
AlphaMissense	0.995	likely pathogenic ✓ concordant with ClinVar
REVEL	0.589	indeterminate
SaProt	LLR -13.74	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP 0.67, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 95 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	24.6	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

No allele count reported in gnomAD v4.1 (AN 1,315,704). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAFA
Protein: p.Ser64Phe
Coding: c.191C>T
MANE Select: NM_201589
dbSNP: rs1554635488
Type: single nucleotide variant
Location: chr8:143430216 (GRCh38)
Structure: AlphaFold pLDDT 64.06 · 1 PDB
Residue 64: a UniProt-annotated variant site (in insdm; may prevent phosphorylation at s-65; may enhance protein stability); the 'disordered' region

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

Disease context

islet cell adenomatosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAFA p.Ala211Thr Uncertain significance ★★ ⚠ same condition
MAFA p.Thr57Arg Pathogenic ★ same condition
MAFA p.Ala138Glu Uncertain significance ★ ⚠ same condition
MAFA p.Phe41Val Uncertain significance ★ ⚠ same condition
MAFA p.Ser61Phe Uncertain significance ★ ⚠ same condition
MAFA p.Gly266Cys Benign ★ same condition
MAFA p.His206_His208del Uncertain significance ★ same condition
MAFA p.Arg333Trp 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/mafa-p-ser64phe (accessed [today's date]).

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