Is MAF p.Ala148Ser (c.442G>T) pathogenic?

MAF p.Ala148Ser (c.442G>T) is classified Uncertain significance in MAF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.0604); Rare (popmax 0.131%, sas); Associated with cataract 21 multiple types.

What condition is associated with MAF p.Ala148Ser (c.442G>T)?

MAF p.Ala148Ser (c.442G>T) is associated with cataract 21 multiple types, Ayme-Gripp syndrome (ClinVar).

How common is MAF p.Ala148Ser (c.442G>T) in the general population?

MAF p.Ala148Ser (c.442G>T) is rare (popmax 0.131%, sas) (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.Ala148Ser (c.442G>T)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

MAF p.Ala148Ser

c.442G>T · rs758854502 · VCV2433601

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.131%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 21 multiple types

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -7.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.69	GERP -3.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 679 bp · p 0.14 · regional, not allelic
Overall
CADD	19.92	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.131% South Asian · 65/49,752 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0958%

Overall 0.00752% 101/1,343,634 alleles · rare exomes 95/1,192,866 · genomes 6/150,768 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.131%	765
Middle Eastern	0.028%	3,574
European (non-Finnish)	0.00331%	30,214

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.Ala148Ser
Coding: c.442G>T
MANE Select: NM_005360
dbSNP: rs758854502
Type: single nucleotide variant
Location: chr16:79599461 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 148: the 'represses are-mediated transcription' 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

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-ala148ser (accessed [today's date]).

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