Is MAFA p.Ser87Ala (c.259T>G) pathogenic?

MAFA p.Ser87Ala (c.259T>G) is classified Likely benign in MAFA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely benign (0.0662); Absent from gnomAD v4.1.

How common is MAFA p.Ser87Ala (c.259T>G) in the general population?

MAFA p.Ser87Ala (c.259T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAFA p.Ser87Ala (c.259T>G)?

AlphaMissense predicts likely benign (score 0.0662) — an in-silico prediction, not a clinical call.

MAFA p.Ser87Ala

c.259T>G · rs2537672029 · VCV2569378

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0662 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0662	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -2.1, phastCons 0.96
Regional constraint	o/e 1.07	unconstrained · MANE · 817 bp · p 0.16 · regional, not allelic
Overall
CADD	6.022	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAFA
Protein: p.Ser87Ala
Coding: c.259T>G
MANE Select: NM_201589
dbSNP: rs2537672029
Type: single nucleotide variant
Location: chr8:143430148 (GRCh38)
Structure: AlphaFold pLDDT 64.06 · 1 PDB
Residue 87: the 'disordered' region

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-ser87ala (accessed [today's date]).

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