Is AGPS p.Asp535Glu (c.1605C>A) pathogenic?

AGPS p.Asp535Glu (c.1605C>A) is classified Uncertain significance in AGPS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). AlphaMissense: likely pathogenic (0.6894); Very rare (popmax 0.0023%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGPS p.Asp535Glu (c.1605C>A)?

AGPS p.Asp535Glu (c.1605C>A) is associated with Inborn genetic diseases (ClinVar).

How common is AGPS p.Asp535Glu (c.1605C>A) in the general population?

AGPS p.Asp535Glu (c.1605C>A) is very rare (popmax 0.0023%, nfe) (gnomAD).

What do computational predictors say about AGPS p.Asp535Glu (c.1605C>A)?

AlphaMissense predicts likely pathogenic (score 0.6894) — an in-silico prediction, not a clinical call.

AGPS p.Asp535Glu

c.1605C>A · rs769160764 · VCV2214212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6894 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0023%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6894	likely pathogenic
REVEL	0.589	indeterminate
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.56 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 145 kb · p 9.9e-28 · 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 0.0023% European (non-Finnish) · 27/1,175,282 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00168% 27/1,608,518 alleles · very rare

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.Asp535Glu
Coding: c.1605C>A
MANE Select: NM_003659
dbSNP: rs769160764
Type: single nucleotide variant
Location: chr2:177508029 (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.Asp590His 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

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-asp535glu (accessed [today's date]).

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