Is AGPAT2 p.Arg90Pro (c.269G>C) pathogenic?

AGPAT2 p.Arg90Pro (c.269G>C) is classified Uncertain significance in AGPAT2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-19). AlphaMissense: likely benign (0.2745); Very rare (popmax 0.00619%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGPAT2 p.Arg90Pro (c.269G>C)?

AGPAT2 p.Arg90Pro (c.269G>C) is associated with Inborn genetic diseases, congenital generalized lipodystrophy type 1 (ClinVar).

How common is AGPAT2 p.Arg90Pro (c.269G>C) in the general population?

AGPAT2 p.Arg90Pro (c.269G>C) is very rare (popmax 0.00619%, nfe) (gnomAD).

What do computational predictors say about AGPAT2 p.Arg90Pro (c.269G>C)?

AlphaMissense predicts likely benign (score 0.2745) — an in-silico prediction, not a clinical call.

AGPAT2 p.Arg90Pro

c.269G>C · rs142176861 · VCV1338051

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2745 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00619%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2745	likely benign
REVEL	0.356	indeterminate
SaProt	LLR -9.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -4.2
Regional constraint	o/e 1.05	unconstrained · MANE · 14 kb · p 0.31 · regional, not allelic
Overall
CADD	1.622	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00619% European (non-Finnish) · 73/1,179,968 alleles

Filtering AF 0.00503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00462%

Overall 0.00477% 77/1,612,990 alleles · very rare exomes 73/1,460,730 · genomes 4/152,260 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00619%	16,164
Remaining individualsnot grpmax-eligible	0.0032%	31,233
Admixed American	0.00167%	60,014
South Asian	0.0011%	91,094

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: AGPAT2
Protein: p.Arg90Pro
Coding: c.269G>C
MANE Select: NM_006412
dbSNP: rs142176861
Type: single nucleotide variant
Location: chr9:136677470 (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

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

Also linked: congenital generalized lipodystrophy type 1

Similar variants

AGPAT2 p.Arg90His Conflicting classifications of pathogenicity ★ ⚠ same residue
AGPAT2 p.Arg90Leu 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

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-arg90pro (accessed [today's date]).

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