Is PKM p.Asp24= (c.72C>T) pathogenic?

PKM p.Asp24= (c.72C>T) is classified Likely benign in PKM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). Ultra-rare (popmax 0.0267%, eas).

How common is PKM p.Asp24= (c.72C>T) in the general population?

PKM p.Asp24= (c.72C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

PKM p.Asp24=

c.72C>T · VCV3307048

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.642	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Overall
CADD	11.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,878 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.000743% 12/1,614,196 alleles · ultra-rare exomes 12/1,461,866 · genomes 0/152,330 · 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: PKM
Protein: p.Asp24=
Coding: c.72C>T
MANE Select: NM_002654
Type: single nucleotide variant
Location: chr15:72219026 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 96.94 · 61 PDB
Residue 24: a β-strand

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

Similar variants

PKM p.Ile265Val Uncertain significance ★★ ⚠ same type
PKM p.Asn146= Benign ★★ same type
PKM p.Leu203= Benign ★★ same type
PKM p.Thr143= Benign ★★ same type
PKM p.Ala419Val Uncertain significance ★ ⚠ same type
PKM p.Ala8Thr Uncertain significance ★ ⚠ same type
PKM p.Ala99Gly Uncertain significance ★ ⚠ same type
PKM p.Arg106Gln 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/pkm-p-asp24 (accessed [today's date]).

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