Is PGK2 p.Val27Phe (c.79G>T) pathogenic?

PGK2 p.Val27Phe (c.79G>T) is classified Uncertain significance in PGK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely pathogenic (0.982); Very rare (popmax 0.0011%, sas).

How common is PGK2 p.Val27Phe (c.79G>T) in the general population?

PGK2 p.Val27Phe (c.79G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PGK2 p.Val27Phe (c.79G>T)?

AlphaMissense predicts likely pathogenic (score 0.982) — an in-silico prediction, not a clinical call.

PGK2 p.Val27Phe

c.79G>T · VCV4135311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.982	likely pathogenic · top 10% in PGK2
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -14.92	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 3.9	GERP 1, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 1,250 bp · p 0.00031 · regional, not allelic
Overall
CADD	25.7	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 · 1/91,072 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,613,460 alleles · very rare exomes 2/1,461,354 · genomes 3/152,106 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	0.000254%	393,205

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val27Phe
Coding: c.79G>T
MANE Select: NM_138733
Type: single nucleotide variant
Location: chr6:49787109 (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-val27phe (accessed [today's date]).

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