Is MAF p.Pro69Arg (c.206C>G) pathogenic?

MAF p.Pro69Arg (c.206C>G) is classified Likely pathogenic in MAF (ClinVar, Single submitter, 3 submitters; last evaluated 2016-09-22). AlphaMissense: likely pathogenic (0.9956); Absent from gnomAD v4.1; Associated with Ayme-Gripp syndrome.

What condition is associated with MAF p.Pro69Arg (c.206C>G)?

MAF p.Pro69Arg (c.206C>G) is associated with Ayme-Gripp syndrome (ClinVar).

How common is MAF p.Pro69Arg (c.206C>G) in the general population?

MAF p.Pro69Arg (c.206C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAF p.Pro69Arg (c.206C>G)?

AlphaMissense predicts likely pathogenic (score 0.9956) — an in-silico prediction, not a clinical call.

MAF p.Pro69Arg

c.206C>G · rs727502768 · VCV162518

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9956 · 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	0.9956	likely pathogenic ✓ concordant with ClinVar
REVEL	0.881	moderately pathogenic-leaning
SaProt	LLR -12.23	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 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	27.4	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.Pro69Arg
Coding: c.206C>G
MANE Select: NM_005360
dbSNP: rs727502768
Type: single nucleotide variant
Location: chr16:79599697 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 69: the 'disordered' region; a UniProt-annotated variant site (in aygrp)

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

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.Pro59His Pathogenic/Likely pathogenic ★★ same condition
MAF p.Ser54Leu Pathogenic ★★ same condition
MAF p.Ser66Leu Pathogenic ★★ same condition
MAF p.Thr58Ile Pathogenic ★★ same condition
MAF p.Thr62Met Likely 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-pro69arg (accessed [today's date]).

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