Is AGPS p.Asp590His (c.1768G>C) pathogenic?

AGPS p.Asp590His (c.1768G>C) is classified Uncertain significance in AGPS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-25). AlphaMissense: ambiguous (0.3442); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with AGPS p.Asp590His (c.1768G>C)?

AGPS p.Asp590His (c.1768G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AGPS p.Asp590His (c.1768G>C) in the general population?

AGPS p.Asp590His (c.1768G>C) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about AGPS p.Asp590His (c.1768G>C)?

AlphaMissense predicts ambiguous (score 0.3442) — an in-silico prediction, not a clinical call.

AGPS p.Asp590His

c.1768G>C · rs370003716 · VCV2059459

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3442 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3442	ambiguous
REVEL	0.791	moderately pathogenic-leaning
SaProt	LLR -8.41	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 145 kb · p 9.9e-28 · regional, not allelic
Overall
CADD	29.4	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 0.0107% African / African-American · 8/74,910 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000867% 14/1,613,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,364
East Asian	0.00891%	11,222
Remaining individualsnot grpmax-eligible	0.0016%	62,476
South Asian	0.0011%	91,076

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: AGPS
Protein: p.Asp590His
Coding: c.1768G>C
MANE Select: NM_003659
dbSNP: rs370003716
Type: single nucleotide variant
Location: chr2:177521339 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.27

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGPS p.Arg265Gln Uncertain significance ★★ ⚠ same condition
AGPS p.Asn649Ser Uncertain significance ★★ ⚠ same condition
AGPS p.Gly9Ala Uncertain significance ★★ ⚠ same condition
AGPS p.Leu120Val Uncertain significance ★★ ⚠ same condition
AGPS p.Phe450Leu Uncertain significance ★★ ⚠ same condition
AGPS p.Pro415Leu Uncertain significance ★★ ⚠ same condition
AGPS p.Pro460Ser Uncertain significance ★★ ⚠ same condition
AGPS p.Thr72Ala Uncertain significance ★★ ⚠ 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/agps-p-asp590his (accessed [today's date]).

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