Is MAF p.Ser61Arg (c.183C>G) pathogenic?

MAF p.Ser61Arg (c.183C>G) is classified Likely pathogenic in MAF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with Ayme-Gripp syndrome.

What condition is associated with MAF p.Ser61Arg (c.183C>G)?

MAF p.Ser61Arg (c.183C>G) is associated with Ayme-Gripp syndrome (ClinVar).

How common is MAF p.Ser61Arg (c.183C>G) in the general population?

MAF p.Ser61Arg (c.183C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAF p.Ser61Arg (c.183C>G)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

MAF p.Ser61Arg

c.183C>G · VCV4855944

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · 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	0.9996	likely pathogenic ✓ concordant with ClinVar · top 6% in MAF
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -13.46	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.25	constrained · MANE · 33 bp · p 0.0024 · regional, not allelic
Overall
CADD	32.0	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.Ser61Arg
Coding: c.183C>G
MANE Select: NM_005360
Type: single nucleotide variant
Location: chr16:79599720 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 61: the 'disordered' 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

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-ser61arg (accessed [today's date]).

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