Is MAF p.Cys46= (c.138C>T) pathogenic?

MAF p.Cys46= (c.138C>T) is classified Likely benign in MAF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). Ultra-rare (popmax 0.0167%, amr); Associated with cataract 21 multiple types.

What condition is associated with MAF p.Cys46= (c.138C>T)?

MAF p.Cys46= (c.138C>T) is associated with cataract 21 multiple types, Ayme-Gripp syndrome (ClinVar).

How common is MAF p.Cys46= (c.138C>T) in the general population?

MAF p.Cys46= (c.138C>T) is ultra-rare (popmax 0.0167%, amr) (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.

MAF p.Cys46=

c.138C>T · rs748965258 · VCV2922656

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Conditions

cataract 21 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -1.8, phastCons 1
Overall
CADD	12.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,012 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00347% 56/1,612,982 alleles · ultra-rare exomes 54/1,460,830 · genomes 2/152,152 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,001
European (non-Finnish)	0.00381%	26,221
African / African-American	0.00133%	74,912

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: MAF
Protein: p.Cys46=
Coding: c.138C>T
MANE Select: NM_005360
dbSNP: rs748965258
Type: single nucleotide variant
Location: chr16:79599765 (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-cys46 (accessed [today's date]).

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