Is MAF p.Pro103His (c.308C>A) pathogenic?

MAF p.Pro103His (c.308C>A) is classified Likely benign in MAF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: likely pathogenic (0.9421); Rare (popmax 0.171%, afr); Associated with Ayme-Gripp syndrome.

What condition is associated with MAF p.Pro103His (c.308C>A)?

MAF p.Pro103His (c.308C>A) is associated with Ayme-Gripp syndrome, cataract 21 multiple types (ClinVar).

How common is MAF p.Pro103His (c.308C>A) in the general population?

MAF p.Pro103His (c.308C>A) is rare (popmax 0.171%, afr) (gnomAD).

What do computational predictors say about MAF p.Pro103His (c.308C>A)?

AlphaMissense predicts likely pathogenic (score 0.9421) — an in-silico prediction, not a clinical call.

MAF p.Pro103His

c.308C>A · rs200484908 · VCV2024686

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9421 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.171%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ayme-Gripp syndrome

Computational evidence

Protein change
AlphaMissense	0.9421	likely pathogenic
REVEL	0.669	pathogenic-leaning
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 1.4, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 679 bp · p 0.14 · regional, not allelic
Overall
CADD	29.9	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

Grpmax group 0.171% African / African-American · 128/74,872 alleles

Filtering AF 0.147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.138%

Overall 0.00932% 150/1,608,602 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.171%	585
Middle Eastern	0.0165%	6,060
Admixed American	0.0118%	8,501
Remaining individualsnot grpmax-eligible	0.0112%	8,891
European (non-Finnish)	0.000594%	168,342

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.Pro103His
Coding: c.308C>A
MANE Select: NM_005360
dbSNP: rs200484908
Type: single nucleotide variant
Location: chr16:79599595 (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

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

Also linked: cataract 21 multiple types

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-pro103his (accessed [today's date]).

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