Is AMZ1 p.Ala236Ser (c.706G>T) pathogenic?

AMZ1 p.Ala236Ser (c.706G>T) is classified Uncertain significance in AMZ1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: likely benign (0.0841); Very rare (popmax 0.00204%, amr).

How common is AMZ1 p.Ala236Ser (c.706G>T) in the general population?

AMZ1 p.Ala236Ser (c.706G>T) is very rare (popmax 0.00204%, amr) (gnomAD).

What do computational predictors say about AMZ1 p.Ala236Ser (c.706G>T)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

AMZ1 p.Ala236Ser

c.706G>T · VCV3537153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00204%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.67	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 0.55	GERP -2.8
Regional constraint	o/e 1.53	unconstrained · MANE · 12 kb · p 2.2e-43 · regional, not allelic
Overall
CADD	0.32	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 0.00204% Admixed American · 1/48,946 alleles

Filtering AF 0.000632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000487%

Overall 0.000907% 14/1,544,206 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00204%	48,946
European (non-Finnish)	0.00113%	88,252

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: AMZ1
Protein: p.Ala236Ser
Coding: c.706G>T
MANE Select: NM_001384743
Type: single nucleotide variant
Location: chr7:2709179 (GRCh38)
Gene constraint: LOEUF 1.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.62

Full AMZ1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMZ1 p.Arg481Ter Likely benign ★★ same type
AMZ1 p.Pro394Leu Likely benign ★★ same type
AMZ1 p.Ala122Pro Uncertain significance ★ ⚠ same type
AMZ1 p.Ala172Val Uncertain significance ★ ⚠ same type
AMZ1 p.Ala188Asp Uncertain significance ★ ⚠ same type
AMZ1 p.Ala208Ser Uncertain significance ★ ⚠ same type
AMZ1 p.Ala208Thr Uncertain significance ★ ⚠ same type
AMZ1 p.Ala230Val 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/amz1-p-ala236ser (accessed [today's date]).

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