Is MAF p.Arg48Pro (c.143G>C) pathogenic?

MAF p.Arg48Pro (c.143G>C) is classified Uncertain significance in MAF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely pathogenic (0.9365); Absent from gnomAD v4.1; Associated with cataract 21 multiple types.

What condition is associated with MAF p.Arg48Pro (c.143G>C)?

MAF p.Arg48Pro (c.143G>C) is associated with cataract 21 multiple types, Ayme-Gripp syndrome (ClinVar).

How common is MAF p.Arg48Pro (c.143G>C) in the general population?

MAF p.Arg48Pro (c.143G>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.Arg48Pro (c.143G>C)?

AlphaMissense predicts likely pathogenic (score 0.9365) — an in-silico prediction, not a clinical call.

MAF p.Arg48Pro

c.143G>C · VCV4784497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9365 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,124)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 21 multiple types

Computational evidence

Protein change
AlphaMissense	0.9365	likely pathogenic
REVEL	0.725	pathogenic-leaning
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.91, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 162 bp · p 0.26 · regional, not allelic
Overall
CADD	28.7	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 1,613,124). 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: MAF
Protein: p.Arg48Pro
Coding: c.143G>C
MANE Select: NM_005360
Type: single nucleotide variant
Location: chr16:79599760 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21

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

Also linked: Ayme-Gripp syndrome

For Early onset non-syndromic cataract (Orphanet):

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

Similar variants

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.Pro59His Pathogenic/Likely pathogenic ★★ same condition
MAF p.Ser54Leu Pathogenic ★★ same condition
MAF p.Ser66Leu Pathogenic ★★ same condition
MAF p.Thr58Ile Pathogenic ★★ 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-arg48pro (accessed [today's date]).

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