Is GPAT2 p.Pro45= (c.135C>T) pathogenic?

GPAT2 p.Pro45= (c.135C>T) is classified Benign in GPAT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-17). Common (popmax 14.1%, eas) — too common for a highly-penetrant pathogenic allele.

GPAT2 p.Pro45=

Q: How common is GPAT2 p.Pro45= (c.135C>T) in the general population?

GPAT2 p.Pro45= (c.135C>T) is common (popmax 14.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.135C>T · rs76666665 · VCV771336

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 14.1%, eas) — too common for a highly-penetrant pathogenic allele

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 0.59	GERP 1.3, phastCons 0.99
Overall
CADD	12.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.1% East Asian · 6,140/43,488 alleles

Filtering AF 13.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.7%

Overall 2.65% 40,659/1,536,734 alleles · common exomes 34,498/1,395,594 · genomes 6,161/141,140 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	14.1%	7
Admixed American	11.4%	9
African / African-American	7.6%	13
Ashkenazi Jewishnot grpmax-eligible	4.39%	23
Remaining individualsnot grpmax-eligible	3.77%	27
South Asian	3.07%	33
Middle Eastern	2.68%	37
Finnishnot grpmax-eligible	2.14%	47
European (non-Finnish)	1.36%	74

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: GPAT2
Protein: p.Pro45=
Coding: c.135C>T
MANE Select: NM_001321527
dbSNP: rs76666665
Type: single nucleotide variant
Location: chr2:96032075 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.38

Full GPAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPAT2 p.Pro45Leu Uncertain significance ★ ⚠ same residue
GPAT2 c.1156-1G>A Likely pathogenic ★ same type
GPAT2 p.Arg627Trp Likely pathogenic ★ ⚠ same type
GPAT2 p.Arg652Ter Likely pathogenic ★ same type
GPAT2 p.Ala459Val Uncertain significance ★ same type
GPAT2 p.Ala636Thr Uncertain significance ★ ⚠ same type
GPAT2 p.Ala736Thr Uncertain significance ★ ⚠ same type
GPAT2 p.Ala738Thr 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/gpat2-p-pro45 (accessed [today's date]).

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