Is MAF p.Leu289Gln (c.866T>A) pathogenic?

MAF p.Leu289Gln (c.866T>A) is classified Uncertain significance in MAF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-31). AlphaMissense: likely pathogenic (0.999); Absent from gnomAD v4.1; Associated with Ayme-Gripp syndrome.

What condition is associated with MAF p.Leu289Gln (c.866T>A)?

MAF p.Leu289Gln (c.866T>A) is associated with Ayme-Gripp syndrome, cataract 21 multiple types (ClinVar).

How common is MAF p.Leu289Gln (c.866T>A) in the general population?

MAF p.Leu289Gln (c.866T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAF p.Leu289Gln (c.866T>A)?

AlphaMissense predicts likely pathogenic (score 0.999) — an in-silico prediction, not a clinical call.

MAF p.Leu289Gln

c.866T>A · rs777544349 · VCV2001513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ayme-Gripp syndrome

Computational evidence

Protein change
AlphaMissense	0.999	likely pathogenic · top 10% in MAF
REVEL	0.861	moderately pathogenic-leaning
SaProt	LLR -14.66	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 11	GERP 2.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 679 bp · p 0.14 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Leu289Gln
Coding: c.866T>A
MANE Select: NM_005360
dbSNP: rs777544349
Type: single nucleotide variant
Location: chr16:79599037 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 289: 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

Ayme-Gripp syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cataract 21 multiple types

Similar variants

MAF p.Leu289Arg Uncertain significance ★ ⚠ same residue
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

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-leu289gln (accessed [today's date]).

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