Is MAZ p.Ala166Val (c.497C>T) pathogenic?

MAZ p.Ala166Val (c.497C>T) is classified Uncertain significance in MAZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). AlphaMissense: likely benign (0.1759); Ultra-rare (popmax 0.0156%, nfe).

How common is MAZ p.Ala166Val (c.497C>T) in the general population?

MAZ p.Ala166Val (c.497C>T) is ultra-rare (popmax 0.0156%, nfe) (gnomAD).

What do computational predictors say about MAZ p.Ala166Val (c.497C>T)?

AlphaMissense predicts likely benign (score 0.1759) — an in-silico prediction, not a clinical call.

MAZ p.Ala166Val

c.497C>T · VCV3293495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1759 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1759	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.98, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 894 bp · p 1.4e-11 · regional, not allelic
Overall
CADD	20.1	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 0.0156% European (non-Finnish) · 179/1,147,388 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.0123% 189/1,541,274 alleles · ultra-rare exomes 175/1,389,762 · genomes 14/151,512 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0156%	6,410
Finnishnot grpmax-eligible	0.00705%	14,179
African / African-American	0.00563%	17,774
Remaining individualsnot grpmax-eligible	0.00335%	29,867

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.Ala166Val
Coding: c.497C>T
MANE Select: NM_002383
Type: single nucleotide variant
Location: chr16:29807282 (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.Ala166Gly Uncertain significance ★ ⚠ same residue
MAZ p.Ala166Thr 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

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-ala166val (accessed [today's date]).

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