Is MAF p.His87Pro (c.260A>C) pathogenic?

MAF p.His87Pro (c.260A>C) is classified Uncertain significance in MAF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-12). AlphaMissense: likely benign (0.1468); Very rare (popmax 0.000339%, nfe); Associated with cataract 21 multiple types.

What condition is associated with MAF p.His87Pro (c.260A>C)?

MAF p.His87Pro (c.260A>C) is associated with cataract 21 multiple types, Ayme-Gripp syndrome (ClinVar).

How common is MAF p.His87Pro (c.260A>C) in the general population?

MAF p.His87Pro (c.260A>C) is very rare (popmax 0.000339%, nfe) (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.His87Pro (c.260A>C)?

AlphaMissense predicts likely benign (score 0.1468) — an in-silico prediction, not a clinical call.

MAF p.His87Pro

c.260A>C · rs1031812704 · VCV2937188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1468 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

cataract 21 multiple types

Computational evidence

Protein change
AlphaMissense	0.1468	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -5.05	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 0.18, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 679 bp · p 0.14 · regional, not allelic
Overall
CADD	23.7	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 0.000339% European (non-Finnish) · 4/1,179,478 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,611,430 alleles · very rare exomes 3/1,459,576 · genomes 1/151,854 · joint denominator

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.His87Pro
Coding: c.260A>C
MANE Select: NM_005360
dbSNP: rs1031812704
Type: single nucleotide variant
Location: chr16:79599643 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21

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-his87pro (accessed [today's date]).

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