Is MAF p.Arg294Trp (c.880C>T) pathogenic?

MAF p.Arg294Trp (c.880C>T) is classified Likely pathogenic in MAF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2015-01-09). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Developmental cataract.

What condition is associated with MAF p.Arg294Trp (c.880C>T)?

MAF p.Arg294Trp (c.880C>T) is associated with Developmental cataract (ClinVar).

How common is MAF p.Arg294Trp (c.880C>T) in the general population?

MAF p.Arg294Trp (c.880C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAF p.Arg294Trp (c.880C>T)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

MAF p.Arg294Trp

c.880C>T · rs864309695 · VCV217344

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Developmental cataract

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 6% in MAF
REVEL	0.954	strongly pathogenic-leaning
SaProt	LLR -15.50	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	35.0	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.Arg294Trp
Coding: c.880C>T
MANE Select: NM_005360
dbSNP: rs864309695
Type: single nucleotide variant
Location: chr16:79599023 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 294: 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

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

Similar variants

MAF p.Arg294= Benign/Likely benign ★★ same residue
MAF p.Arg294Gln Pathogenic ★ same residue
MAF p.Pro63Arg Likely pathogenic ★ same condition
MAF p.Cys305= Likely pathogenic same condition
MAF p.Glu273Asp Likely pathogenic ⚠ same condition
MAF p.Ala302Val Pathogenic/Likely pathogenic ★★ same type
MAF p.Arg299Cys Pathogenic/Likely pathogenic ★★ same type
MAF p.Arg306Gly Pathogenic/Likely pathogenic ★★ same type

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-arg294trp (accessed [today's date]).

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