Is MAF p.Arg299Ser (c.895C>A) pathogenic?

MAF p.Arg299Ser (c.895C>A) is classified Likely pathogenic in MAF (ClinVar, Single submitter, 2 submitters; last evaluated 2020-07-18). AlphaMissense: likely pathogenic (1); No allele count reported in gnomAD v4.1 (AN 1,613,490); Associated with cataract 21 multiple types.

What condition is associated with MAF p.Arg299Ser (c.895C>A)?

MAF p.Arg299Ser (c.895C>A) is associated with cataract 21 multiple types (ClinVar).

How common is MAF p.Arg299Ser (c.895C>A) in the general population?

MAF p.Arg299Ser (c.895C>A) is no allele count reported in gnomAD v4.1 (AN 1,613,490) (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.Arg299Ser (c.895C>A)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

MAF p.Arg299Ser

c.895C>A · rs786205221 · VCV190235

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,490)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 21 multiple types

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic ✓ concordant with ClinVar · top 6% in MAF
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -16.65	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 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.20	constrained · MANE · 65 bp · p 9.5e-06 · 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

No allele count reported in gnomAD v4.1 (AN 1,613,490). 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.Arg299Ser
Coding: c.895C>A
MANE Select: NM_005360
dbSNP: rs786205221
Type: single nucleotide variant
Location: chr16:79599008 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 299: the bzip domain; 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.Arg299Cys Pathogenic/Likely pathogenic ★★ same residue
MAF p.Arg299= Likely benign ★ same residue
MAF p.Arg299Gly Uncertain significance ⚠ same residue
MAF p.Ala302Val 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-arg299ser (accessed [today's date]).

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