Is AGPS c.1233+1G>A pathogenic?

AGPS c.1233+1G>A is classified Likely pathogenic in AGPS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). Very rare (popmax 8.91e-05%, nfe).

How common is AGPS c.1233+1G>A in the general population?

AGPS c.1233+1G>A is very rare (popmax 8.91e-05%, nfe) (gnomAD).

AGPS c.1233+1G>A

rs2105693633 · VCV1418693

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.91e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function in a LoF-intolerant gene
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ0.99	donor loss · deltas
Pangolin	Δ0.87	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.2	GERP 0.99, phastCons 1
Non-coding constraint	Z 0.23	1 kb window · o/e 0.98 · regional · uncalibrated
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.91e-05% European (non-Finnish) · 1/1,121,866 alleles

Overall 7.26e-05% 1/1,377,870 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
Coding: c.1233+1G>A
MANE Select: NM_003659
dbSNP: rs2105693633
Type: single nucleotide variant
Location: chr2:177482187 (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

Similar variants

AGPS p.Arg182Ter Pathogenic/Likely pathogenic ★★ same type
AGPS p.Thr309Ile Likely pathogenic ★★ same type
AGPS c.1855+6C>A Uncertain significance ★★ same type
AGPS c.*118A>G Uncertain significance ★★ same type
AGPS p.Arg265Gln Uncertain significance ★★ ⚠ same type
AGPS p.Asn649Ser Uncertain significance ★★ ⚠ same type
AGPS p.Asp28Val Uncertain significance ★★ ⚠ same type
AGPS p.Asp590His 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/agps-c-1233-plus-1g-a (accessed [today's date]).

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