Is MAFA p.Phe41Val (c.121T>G) pathogenic?

MAFA p.Phe41Val (c.121T>G) is classified Uncertain significance in MAFA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). AlphaMissense: likely benign (0.2705); Very rare (popmax 0.00496%, sas); Associated with islet cell adenomatosis.

What condition is associated with MAFA p.Phe41Val (c.121T>G)?

MAFA p.Phe41Val (c.121T>G) is associated with islet cell adenomatosis (ClinVar).

How common is MAFA p.Phe41Val (c.121T>G) in the general population?

MAFA p.Phe41Val (c.121T>G) is very rare (popmax 0.00496%, sas) (gnomAD).

What do computational predictors say about MAFA p.Phe41Val (c.121T>G)?

AlphaMissense predicts likely benign (score 0.2705) — an in-silico prediction, not a clinical call.

MAFA p.Phe41Val

c.121T>G · rs2537672277 · VCV1803218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00496%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

islet cell adenomatosis

Computational evidence

Protein change
AlphaMissense	0.2705	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -3.7, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 144 bp · p 0.37 · regional, not allelic
Overall
CADD	17.22	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00496% South Asian · 4/80,644 alleles

Filtering AF 0.00166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00098%

Overall 0.000276% 4/1,449,276 alleles · very rare exomes 4/1,301,274 · genomes 0/148,002 · joint denominator

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: MAFA
Protein: p.Phe41Val
Coding: c.121T>G
MANE Select: NM_201589
dbSNP: rs2537672277
Type: single nucleotide variant
Location: chr8:143430286 (GRCh38)
Structure: AlphaFold pLDDT 64.06 · 1 PDB
Residue 41: 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.Ser64Phe Likely pathogenic ★ same condition
MAFA p.Thr57Arg Pathogenic ★ same condition
MAFA p.Ala138Glu 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-phe41val (accessed [today's date]).

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