Is AGPAT2 p.Phe78= (c.234C>T) pathogenic?

AGPAT2 p.Phe78= (c.234C>T) is classified Conflicting classifications of pathogenicity in AGPAT2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-09). Ultra-rare (popmax 0.0187%, sas); Associated with congenital generalized lipodystrophy type 1.

What condition is associated with AGPAT2 p.Phe78= (c.234C>T)?

AGPAT2 p.Phe78= (c.234C>T) is associated with congenital generalized lipodystrophy type 1 (ClinVar).

How common is AGPAT2 p.Phe78= (c.234C>T) in the general population?

AGPAT2 p.Phe78= (c.234C>T) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

How is Congenital generalized lipodystrophy inherited?

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

AGPAT2 p.Phe78=

c.234C>T · rs543374987 · VCV365931

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Conditions

congenital generalized lipodystrophy type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -4.2
Overall
CADD	1.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/91,082 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00976%

Overall 0.0026% 42/1,613,046 alleles · ultra-rare exomes 40/1,460,660 · genomes 2/152,386 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,358
Admixed American	0.00333%	30,018
European (non-Finnish)	0.00178%	56,189
Remaining individualsnot grpmax-eligible	0.0016%	62,488
Finnishnot grpmax-eligible	0.00159%	62,948

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.Phe78=
Coding: c.234C>T
MANE Select: NM_006412
dbSNP: rs543374987
Type: single nucleotide variant
Location: chr9:136677505 (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 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
AGPAT2 p.Glu172Lys Pathogenic/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-phe78 (accessed [today's date]).

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