Is MAFA p.Pro128Ser (c.382C>T) pathogenic?

MAFA p.Pro128Ser (c.382C>T) is classified Uncertain significance in MAFA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely pathogenic (0.8234); Very rare (popmax 0.00246%, nfe).

How common is MAFA p.Pro128Ser (c.382C>T) in the general population?

MAFA p.Pro128Ser (c.382C>T) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about MAFA p.Pro128Ser (c.382C>T)?

AlphaMissense predicts likely pathogenic (score 0.8234) — an in-silico prediction, not a clinical call.

MAFA p.Pro128Ser

c.382C>T · VCV3541960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8234 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8234	likely pathogenic
REVEL	0.52	indeterminate
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 1.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 817 bp · p 0.16 · 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

Grpmax group 0.00246% European (non-Finnish) · 26/1,056,150 alleles

Filtering AF 0.00171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00145%

Overall 0.00196% 27/1,378,142 alleles · very rare exomes 26/1,228,832 · genomes 1/149,310 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,621
South Asian	0.00151%	66,418

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.Pro128Ser
Coding: c.382C>T
MANE Select: NM_201589
Type: single nucleotide variant
Location: chr8:143430025 (GRCh38)
Structure: AlphaFold pLDDT 64.06 · 1 PDB

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

Similar variants

MAFA p.Ala211Thr Uncertain significance ★★ ⚠ same type
MAFA p.Arg333Trp Uncertain significance ★★ ⚠ same type
MAFA p.Arg44His Uncertain significance ★★ same type
MAFA p.Ser64Phe Likely pathogenic ★ same type
MAFA p.Thr57Arg Pathogenic ★ same type
MAFA p.Ala138Glu Uncertain significance ★ ⚠ same type
MAFA p.Ala158Glu Uncertain significance ★ ⚠ same type
MAFA p.Ala159Val 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-pro128ser (accessed [today's date]).

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