Is MAFA p.Pro157Ser (c.469C>T) pathogenic?

MAFA p.Pro157Ser (c.469C>T) is classified Uncertain significance in MAFA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). AlphaMissense: likely benign (0.0896); Ultra-rare (popmax 0.0418%, nfe).

How common is MAFA p.Pro157Ser (c.469C>T) in the general population?

MAFA p.Pro157Ser (c.469C>T) is ultra-rare (popmax 0.0418%, nfe) (gnomAD).

What do computational predictors say about MAFA p.Pro157Ser (c.469C>T)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

MAFA p.Pro157Ser

c.469C>T · VCV3292567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0418%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -7.09	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 7	GERP -1, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 817 bp · p 0.16 · regional, not allelic
Overall
CADD	20.9	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 0.0418% European (non-Finnish) · 421/1,006,690 alleles

Filtering AF 0.0384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0372%

Overall 0.0346% 437/1,261,726 alleles · ultra-rare exomes 418/1,113,790 · genomes 19/147,936 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0418%	2,391
Remaining individualsnot grpmax-eligible	0.0304%	3,290
African / African-American	0.00319%	31,320

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.Pro157Ser
Coding: c.469C>T
MANE Select: NM_201589
Type: single nucleotide variant
Location: chr8:143429938 (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.Pro157Thr Uncertain significance ★ ⚠ same residue
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

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-pro157ser (accessed [today's date]).

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