Is MAFA p.Ser88Ala (c.262T>G) pathogenic?

MAFA p.Ser88Ala (c.262T>G) is classified Likely benign in MAFA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely benign (0.0637); Very rare (popmax 0.000111%, nfe).

How common is MAFA p.Ser88Ala (c.262T>G) in the general population?

MAFA p.Ser88Ala (c.262T>G) is very rare (popmax 0.000111%, nfe) (gnomAD).

What do computational predictors say about MAFA p.Ser88Ala (c.262T>G)?

AlphaMissense predicts likely benign (score 0.0637) — an in-silico prediction, not a clinical call.

MAFA p.Ser88Ala

c.262T>G · rs1819518441 · VCV2569379

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0637 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000111%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0637	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -6.32	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 -0.51	GERP -1.8
Regional constraint	o/e 1.07	unconstrained · MANE · 817 bp · p 0.16 · regional, not allelic
Overall
CADD	7.995	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 0.000111% European (non-Finnish) · 1/900,038 alleles

Overall 9.26e-05% 1/1,080,444 alleles · very rare exomes 1/954,258 · genomes 0/126,186 · 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.Ser88Ala
Coding: c.262T>G
MANE Select: NM_201589
dbSNP: rs1819518441
Type: single nucleotide variant
Location: chr8:143430145 (GRCh38)
Structure: AlphaFold pLDDT 64.06 · 1 PDB
Residue 88: 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-ser88ala (accessed [today's date]).

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