Is MAFA p.Ser98Arg (c.292A>C) pathogenic?

MAFA p.Ser98Arg (c.292A>C) is classified Uncertain significance in MAFA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: ambiguous (0.4408); Very rare (popmax 0.00373%, sas).

How common is MAFA p.Ser98Arg (c.292A>C) in the general population?

MAFA p.Ser98Arg (c.292A>C) is very rare (popmax 0.00373%, sas) (gnomAD).

What do computational predictors say about MAFA p.Ser98Arg (c.292A>C)?

AlphaMissense predicts ambiguous (score 0.4408) — an in-silico prediction, not a clinical call.

MAFA p.Ser98Arg

c.292A>C · rs2537671965 · VCV2218280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4408 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, sas)

Computational evidence

Protein change
AlphaMissense	0.4408	ambiguous
REVEL	0.304	indeterminate
SaProt	LLR -8.03	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.44, phastCons 0.083
Regional constraint	o/e 1.07	unconstrained · MANE · 817 bp · p 0.16 · regional, not allelic
Overall
CADD	14.85	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 0.00373% South Asian · 1/26,774 alleles

Overall 0.000182% 2/1,101,730 alleles · very rare exomes 2/968,090 · genomes 0/133,640 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00373%	26,774
European (non-Finnish)	0.00011%	909,273

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.Ser98Arg
Coding: c.292A>C
MANE Select: NM_201589
dbSNP: rs2537671965
Type: single nucleotide variant
Location: chr8:143430115 (GRCh38)
Structure: AlphaFold pLDDT 64.06 · 1 PDB
Residue 98: the 'disordered' region

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

Similar variants

MAFA p.Ser98Asn 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-ser98arg (accessed [today's date]).

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