Is AGMO p.His408= (c.1224C>T) pathogenic?

AGMO p.His408= (c.1224C>T) is classified Likely benign in AGMO (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Ultra-rare (popmax 0.0892%, eas); Associated with AGMO-related disorder.

What condition is associated with AGMO p.His408= (c.1224C>T)?

AGMO p.His408= (c.1224C>T) is associated with AGMO-related disorder (ClinVar).

How common is AGMO p.His408= (c.1224C>T) in the general population?

AGMO p.His408= (c.1224C>T) is ultra-rare (popmax 0.0892%, eas) (gnomAD).

AGMO p.His408=

c.1224C>T · rs190327309 · VCV3033422

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0892%, eas)

Conditions

AGMO-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.022	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.2, phastCons 1
Overall
CADD	4.454	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0892% East Asian · 40/44,830 alleles

Filtering AF 0.0674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.00384% 62/1,612,836 alleles · ultra-rare exomes 52/1,460,840 · genomes 10/151,996 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0892%	1,121
Remaining individualsnot grpmax-eligible	0.0048%	20,822
Admixed American	0.00167%	59,952
European (non-Finnish)	0.00153%	65,508

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.His408=
Coding: c.1224C>T
MANE Select: NM_001004320
dbSNP: rs190327309
Type: single nucleotide variant
Location: chr7:15365553 (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

Disease context

AGMO-related disorder

Similar variants

AGMO p.Asn207Lys Uncertain significance ★ ⚠ same condition
AGMO p.Leu412Ile Uncertain significance ★ ⚠ same condition
AGMO p.Pro264Ser Uncertain significance ★ ⚠ same condition
AGMO p.Pro302Ser Uncertain significance ⚠ same condition
AGMO p.Ser219Cys Uncertain significance ⚠ same condition
AGMO c.1074+10A>G Likely benign same condition
AGMO p.Leu395Val Benign same condition
AGMO p.Ser280Tyr Benign same condition

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-his408 (accessed [today's date]).

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