Is MAF p.Arg288Pro (c.863G>C) pathogenic?

MAF p.Arg288Pro (c.863G>C) is classified Pathogenic in MAF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2012-03-16). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with cataract 21 multiple types.

What condition is associated with MAF p.Arg288Pro (c.863G>C)?

MAF p.Arg288Pro (c.863G>C) is associated with cataract 21 multiple types (ClinVar).

How common is MAF p.Arg288Pro (c.863G>C) in the general population?

MAF p.Arg288Pro (c.863G>C) is absent from gnomAD v4.1 (gnomAD).

How is Early onset non-syndromic cataract inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MAF p.Arg288Pro (c.863G>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

MAF p.Arg288Pro

c.863G>C · rs121917735 · VCV13231

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 21 multiple types

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 6% in MAF
REVEL	0.759	pathogenic-leaning
SaProt	LLR -14.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 2.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 679 bp · p 0.14 · regional, not allelic
Overall
CADD	34.0	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: MAF
Protein: p.Arg288Pro
Coding: c.863G>C
MANE Select: NM_005360
dbSNP: rs121917735
Type: single nucleotide variant
Location: chr16:79599040 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 288: the bzip domain; a UniProt-annotated variant site (in ctrct21); the 'represses are-mediated transcription' region; the 'basic motif' region

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

Disease context

cataract 21 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

MAF p.Arg288= Likely benign ★★ same residue
MAF p.Arg288Gly Uncertain significance ⚠ same residue
MAF p.Ala302Val Pathogenic/Likely pathogenic ★★ same condition
MAF p.Arg299Cys Pathogenic/Likely pathogenic ★★ same condition
MAF p.Arg306Gly Pathogenic/Likely pathogenic ★★ same condition
MAF p.Cys305Phe Likely pathogenic ★★ same condition
MAF p.Thr62Met Likely pathogenic ★★ same condition
MAF p.Ala148Ser Uncertain significance ★★ ⚠ same condition

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/maf-p-arg288pro (accessed [today's date]).

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