Is PKLR p.Ser562= (c.1686C>T) pathogenic?

PKLR p.Ser562= (c.1686C>T) is classified Benign/Likely benign in PKLR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-01). Rare (popmax 0.792%, amr); Associated with pyruvate kinase deficiency of red cells.

What condition is associated with PKLR p.Ser562= (c.1686C>T)?

PKLR p.Ser562= (c.1686C>T) is associated with pyruvate kinase deficiency of red cells (ClinVar).

How common is PKLR p.Ser562= (c.1686C>T) in the general population?

PKLR p.Ser562= (c.1686C>T) is rare (popmax 0.792%, amr) (gnomAD).

PKLR p.Ser562=

Q: How is Hemolytic anemia due to red cell pyruvate kinase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1686C>T · rs140859641 · VCV292805

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.792%, amr)

Conditions

pyruvate kinase deficiency of red cells

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 -4.5	GERP -4.6
Overall
CADD	5.725	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.792% Admixed American · 475/59,966 alleles

Filtering AF 0.733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.71%

Overall 0.0404% 651/1,613,214 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.792%	126
Remaining individualsnot grpmax-eligible	0.0208%	4,805
European (non-Finnish)	0.0128%	7,811
Finnishnot grpmax-eligible	0.0125%	7,995
African / African-American	0.00401%	24,950
South Asian	0.0011%	91,042

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: PKLR
Protein: p.Ser562=
Coding: c.1686C>T
MANE Select: NM_000298
dbSNP: rs140859641
Type: single nucleotide variant
Location: chr1:155290611 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.75 · 67 PDB
Residue 562: a binding site

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

Disease context

pyruvate kinase deficiency of red cells — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hemolytic anemia due to red cell pyruvate kinase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

PKLR c.1618+1G>A Likely pathogenic ★★ same condition
PKLR c.694+2T>G Pathogenic/Likely pathogenic ★★ same condition
PKLR p.Ala423= Pathogenic/Likely pathogenic ★★ same condition
PKLR p.Arg270Ter Pathogenic ★★ same condition
PKLR p.Arg479His Pathogenic ★★ ⚠ same condition
PKLR p.Arg486Trp Pathogenic/Likely pathogenic ★★ same condition
PKLR p.Arg488Ter Pathogenic ★★ same condition
PKLR p.Arg504Leu Likely pathogenic ★★ same condition

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/pklr-p-ser562 (accessed [today's date]).

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