Is PGK2 p.Asp24His (c.70G>C) pathogenic?

PGK2 p.Asp24His (c.70G>C) is classified Uncertain significance in PGK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-05). AlphaMissense: likely pathogenic (0.9979); Very rare (popmax 0.00439%, sas).

How common is PGK2 p.Asp24His (c.70G>C) in the general population?

PGK2 p.Asp24His (c.70G>C) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about PGK2 p.Asp24His (c.70G>C)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

PGK2 p.Asp24His

c.70G>C · VCV3417380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9979	likely pathogenic · top 1% in PGK2
REVEL	0.907	moderately pathogenic-leaning
SaProt	LLR -17.92	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 1,250 bp · p 0.00031 · regional, not allelic
Overall
CADD	26.2	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 0.00439% South Asian · 4/91,054 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,613,216 alleles · very rare exomes 4/1,461,008 · genomes 0/152,208 · joint denominator

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.Asp24His
Coding: c.70G>C
MANE Select: NM_138733
Type: single nucleotide variant
Location: chr6:49787118 (GRCh38)
Gene constraint: LOEUF 1.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.34
Residue 24: a binding site

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-asp24his (accessed [today's date]).

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