Is MAFA p.Cys69Arg (c.205T>C) pathogenic?

MAFA p.Cys69Arg (c.205T>C) is classified Uncertain significance in MAFA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-23). AlphaMissense: likely pathogenic (0.9334); No allele count reported in gnomAD v4.1 (AN 1,239,314).

How common is MAFA p.Cys69Arg (c.205T>C) in the general population?

MAFA p.Cys69Arg (c.205T>C) is no allele count reported in gnomAD v4.1 (AN 1,239,314) (gnomAD).

What do computational predictors say about MAFA p.Cys69Arg (c.205T>C)?

AlphaMissense predicts likely pathogenic (score 0.9334) — an in-silico prediction, not a clinical call.

MAFA p.Cys69Arg

c.205T>C · rs2537672155 · VCV2528908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9334 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,239,314)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9334	likely pathogenic
REVEL	0.507	indeterminate
SaProt	LLR -5.50	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 8.2	GERP -2, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 95 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	22.5	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

No allele count reported in gnomAD v4.1 (AN 1,239,314). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAFA
Protein: p.Cys69Arg
Coding: c.205T>C
MANE Select: NM_201589
dbSNP: rs2537672155
Type: single nucleotide variant
Location: chr8:143430202 (GRCh38)
Structure: AlphaFold pLDDT 64.06 · 1 PDB
Residue 69: 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-cys69arg (accessed [today's date]).

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