Is AGMO p.Trp111Ser (c.332G>C) pathogenic?

AGMO p.Trp111Ser (c.332G>C) is classified Uncertain significance in AGMO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-30). AlphaMissense: ambiguous (0.4474); Ultra-rare (popmax 0.018%, eas).

How common is AGMO p.Trp111Ser (c.332G>C) in the general population?

AGMO p.Trp111Ser (c.332G>C) is ultra-rare (popmax 0.018%, eas) (gnomAD).

What do computational predictors say about AGMO p.Trp111Ser (c.332G>C)?

AlphaMissense predicts ambiguous (score 0.4474) — an in-silico prediction, not a clinical call.

AGMO p.Trp111Ser

c.332G>C · VCV3842512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4474 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, eas)

Computational evidence

Protein change
AlphaMissense	0.4474	ambiguous
REVEL	0.373	indeterminate
SaProt	LLR -12.69	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.45	unconstrained · MANE · 361 kb · p 3.8e-25 · 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

Grpmax group 0.018% East Asian · 8/44,566 alleles

Filtering AF 0.00889% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00645%

Overall 0.000621% 10/1,609,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.018%	5,571
African / African-American	0.00267%	37,416

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: AGMO
Protein: p.Trp111Ser
Coding: c.332G>C
MANE Select: NM_001004320
Type: single nucleotide variant
Location: chr7:15544849 (GRCh38)
Gene constraint: LOEUF 1.561 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90

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

Similar variants

AGMO p.Trp111Gly Uncertain significance ★ same residue
AGMO p.Arg133Cys Uncertain significance ★★ ⚠ same type
AGMO p.Arg83Gln Uncertain significance ★★ ⚠ same type
AGMO p.Gly238Cys Uncertain significance ★★ ⚠ same type
AGMO p.Gly322Ser Uncertain significance ★★ ⚠ same type
AGMO p.Ile281Val Uncertain significance ★★ ⚠ same type
AGMO p.Leu213Val Uncertain significance ★★ ⚠ same type
AGMO p.Lys234Arg 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/agmo-p-trp111ser (accessed [today's date]).

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