Is AGPAT2 p.Pro263Arg (c.788C>G) pathogenic?

AGPAT2 p.Pro263Arg (c.788C>G) is classified Uncertain significance in AGPAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-16). AlphaMissense: likely benign (0.0882); Absent from gnomAD v4.1; Associated with congenital generalized lipodystrophy type 1.

What condition is associated with AGPAT2 p.Pro263Arg (c.788C>G)?

AGPAT2 p.Pro263Arg (c.788C>G) is associated with congenital generalized lipodystrophy type 1 (ClinVar).

How common is AGPAT2 p.Pro263Arg (c.788C>G) in the general population?

AGPAT2 p.Pro263Arg (c.788C>G) is absent from gnomAD v4.1 (gnomAD).

How is Congenital generalized lipodystrophy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about AGPAT2 p.Pro263Arg (c.788C>G)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

AGPAT2 p.Pro263Arg

c.788C>G · rs17848858 · VCV1803905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital generalized lipodystrophy type 1

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -11.31	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -0.49, phastCons 0.99
Regional constraint	o/e 1.05	unconstrained · MANE · 14 kb · p 0.31 · regional, not allelic
Overall
CADD	19.34	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGPAT2
Protein: p.Pro263Arg
Coding: c.788C>G
MANE Select: NM_006412
dbSNP: rs17848858
Type: single nucleotide variant
Location: chr9:136673801 (GRCh38)
Gene constraint: LOEUF 1.199 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.66

Full AGPAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital generalized lipodystrophy type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital generalized lipodystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

AGPAT2 p.Pro263Leu Uncertain significance ★★ ⚠ same residue
AGPAT2 c.492+1G>A Pathogenic/Likely pathogenic ★★ same condition
AGPAT2 c.493-1G>C Pathogenic/Likely pathogenic ★★ same condition
AGPAT2 c.493-2A>G Likely pathogenic ★★ same condition
AGPAT2 c.589-2A>G Pathogenic ★★ same condition
AGPAT2 c.662-2A>C Pathogenic/Likely pathogenic ★★ same condition
AGPAT2 p.Arg68Ter Pathogenic ★★ same condition
AGPAT2 p.Gln264Ter Likely pathogenic ★★ 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/agpat2-p-pro263arg (accessed [today's date]).

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