Is MAF p.Leu296Pro (c.887T>C) pathogenic?

MAF p.Leu296Pro (c.887T>C) is classified Uncertain significance in MAF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-26). AlphaMissense: likely pathogenic (1); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MAF p.Leu296Pro (c.887T>C)?

MAF p.Leu296Pro (c.887T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MAF p.Leu296Pro (c.887T>C) in the general population?

MAF p.Leu296Pro (c.887T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAF p.Leu296Pro (c.887T>C)?

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

MAF p.Leu296Pro

c.887T>C · rs1913784440 · VCV985458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic · top 6% in MAF
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -15.44	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 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

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.Leu296Pro
Coding: c.887T>C
MANE Select: NM_005360
dbSNP: rs1913784440
Type: single nucleotide variant
Location: chr16:79599016 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 296: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAF p.Arg306Gly Pathogenic/Likely pathogenic ★★ same condition
MAF p.Ser57Phe Likely pathogenic ★★ same condition
MAF p.His394Leu Uncertain significance ★★ same condition
WWOX p.Ala388Val Uncertain significance ★★ ⚠ same condition
WWOX p.Ala399Thr Uncertain significance ★★ ⚠ same condition
WWOX p.Arg395Trp Uncertain significance ★★ ⚠ same condition
WWOX p.Glu391Gly Uncertain significance ★★ ⚠ same condition
WWOX p.Glu402Gln 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-leu296pro (accessed [today's date]).

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