Is MAF p.Ala75Val (c.224C>T) pathogenic?

MAF p.Ala75Val (c.224C>T) is classified Uncertain significance in MAF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-23). AlphaMissense: likely pathogenic (0.6633); No allele count reported in gnomAD v4.1 (AN 1,612,218); Associated with Ayme-Gripp syndrome.

What condition is associated with MAF p.Ala75Val (c.224C>T)?

MAF p.Ala75Val (c.224C>T) is associated with Ayme-Gripp syndrome (ClinVar).

How common is MAF p.Ala75Val (c.224C>T) in the general population?

MAF p.Ala75Val (c.224C>T) is no allele count reported in gnomAD v4.1 (AN 1,612,218) (gnomAD).

What do computational predictors say about MAF p.Ala75Val (c.224C>T)?

AlphaMissense predicts likely pathogenic (score 0.6633) — an in-silico prediction, not a clinical call.

MAF p.Ala75Val

c.224C>T · rs1913879694 · VCV983347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6633 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,218)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Ayme-Gripp syndrome

Computational evidence

Protein change
AlphaMissense	0.6633	likely pathogenic
REVEL	0.466	indeterminate
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP -4, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 679 bp · p 0.14 · regional, not allelic
Overall
CADD	26.7	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

No allele count reported in gnomAD v4.1 (AN 1,612,218). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAF
Protein: p.Ala75Val
Coding: c.224C>T
MANE Select: NM_005360
dbSNP: rs1913879694
Type: single nucleotide variant
Location: chr16:79599679 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.21
Residue 75: 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-ala75val (accessed [today's date]).

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