Is MAZ p.Pro175Arg (c.524C>G) pathogenic?

MAZ p.Pro175Arg (c.524C>G) is classified Uncertain significance in MAZ (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-27). AlphaMissense: ambiguous (0.5534); Very rare (popmax 0.00227%, sas).

How common is MAZ p.Pro175Arg (c.524C>G) in the general population?

MAZ p.Pro175Arg (c.524C>G) is very rare (popmax 0.00227%, sas) (gnomAD).

What do computational predictors say about MAZ p.Pro175Arg (c.524C>G)?

AlphaMissense predicts ambiguous (score 0.5534) — an in-silico prediction, not a clinical call.

MAZ p.Pro175Arg

c.524C>G · rs780466757 · VCV3124012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5534 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00227%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5534	ambiguous
REVEL	0.045	moderately benign-leaning
SaProt	LLR -10.38	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -0.89, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 894 bp · p 1.4e-11 · regional, not allelic
Overall
CADD	19.23	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 0.00227% South Asian · 2/87,990 alleles

Filtering AF 0.000377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000141%

Overall 0.000189% 3/1,588,752 alleles · very rare exomes 3/1,436,642 · genomes 0/152,110 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00227%	43,995
European (non-Finnish)	8.55e-05%	1,169,420

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: MAZ
Protein: p.Pro175Arg
Coding: c.524C>G
MANE Select: NM_002383
dbSNP: rs780466757
Type: single nucleotide variant
Location: chr16:29807309 (GRCh38)
Gene constraint: LOEUF 0.35 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.37

Full MAZ gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRRT2 p.Ter341Ser Likely pathogenic ★ same type
MAZ c.1279+1G>A Uncertain significance ★ same type
MAZ c.1280-347G>C Uncertain significance ★ same type
MAZ c.1280-351C>T Uncertain significance ★ same type
MAZ c.1280-353G>C Uncertain significance ★ same type
MAZ c.1280-357C>T Uncertain significance ★ same type
MAZ c.1280-376C>T Uncertain significance ★ same type
MAZ c.1280-385G>A Uncertain significance ★ same type

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/maz-p-pro175arg (accessed [today's date]).

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