Is MAZ p.Pro12Ser (c.34C>T) pathogenic?

MAZ p.Pro12Ser (c.34C>T) is classified Uncertain significance in MAZ (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely benign (0.1397); Very rare (popmax 0.00283%, sas).

How common is MAZ p.Pro12Ser (c.34C>T) in the general population?

MAZ p.Pro12Ser (c.34C>T) is very rare (popmax 0.00283%, sas) (gnomAD).

What do computational predictors say about MAZ p.Pro12Ser (c.34C>T)?

AlphaMissense predicts likely benign (score 0.1397) — an in-silico prediction, not a clinical call.

MAZ p.Pro12Ser

c.34C>T · rs530190319 · VCV3124008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00283%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1397	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	GERP -0.56, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 894 bp · p 1.4e-11 · regional, not allelic
Overall
CADD	19.12	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00283% South Asian · 2/70,548 alleles

Filtering AF 0.000607% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000479%

Overall 0.00101% 14/1,390,438 alleles · very rare exomes 13/1,242,904 · genomes 1/147,534 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00283%	35,274
European (non-Finnish)	0.00114%	87,884

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.Pro12Ser
Coding: c.34C>T
MANE Select: NM_002383
dbSNP: rs530190319
Type: single nucleotide variant
Location: chr16:29806735 (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

MAZ p.Pro12Thr Uncertain significance ★ ⚠ same residue
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

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-pro12ser (accessed [today's date]).

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