Is PGK2 p.Ser364Pro (c.1090T>C) pathogenic?

PGK2 p.Ser364Pro (c.1090T>C) is classified Uncertain significance in PGK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.5785); Very rare (popmax 0.0011%, sas).

How common is PGK2 p.Ser364Pro (c.1090T>C) in the general population?

PGK2 p.Ser364Pro (c.1090T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PGK2 p.Ser364Pro (c.1090T>C)?

AlphaMissense predicts likely pathogenic (score 0.5785) — an in-silico prediction, not a clinical call.

PGK2 p.Ser364Pro

c.1090T>C · rs780200740 · VCV2614218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5785 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5785	likely pathogenic
REVEL	0.345	indeterminate
SaProt	LLR -11.94	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP -0.93, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 1,250 bp · p 0.00031 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0011% South Asian · 1/91,090 alleles

Overall 0.000124% 2/1,614,018 alleles · very rare exomes 1/1,461,874 · genomes 1/152,144 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,090
European (non-Finnish)	8.47e-05%	1,180,025

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: PGK2
Protein: p.Ser364Pro
Coding: c.1090T>C
MANE Select: NM_138733
dbSNP: rs780200740
Type: single nucleotide variant
Location: chr6:49786098 (GRCh38)
Gene constraint: LOEUF 1.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.34

Full PGK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGK2 p.Ala102Thr Uncertain significance ★ ⚠ same type
PGK2 p.Ala109Asp Uncertain significance ★ ⚠ same type
PGK2 p.Ala172Thr Uncertain significance ★ ⚠ same type
PGK2 p.Ala210Ser Uncertain significance ★ ⚠ same type
PGK2 p.Ala55Gly Uncertain significance ★ ⚠ same type
PGK2 p.Ala55Ser Uncertain significance ★ ⚠ same type
PGK2 p.Arg171Cys Uncertain significance ★ ⚠ same type
PGK2 p.Arg171His 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/pgk2-p-ser364pro (accessed [today's date]).

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