Is AK1 p.Ser51= (c.153G>A) pathogenic?

AK1 p.Ser51= (c.153G>A) is classified Benign/Likely benign in AK1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-11). Rare (popmax 0.834%, afr); Associated with hemolytic anemia due to adenylate kinase deficiency.

What condition is associated with AK1 p.Ser51= (c.153G>A)?

AK1 p.Ser51= (c.153G>A) is associated with hemolytic anemia due to adenylate kinase deficiency (ClinVar).

How common is AK1 p.Ser51= (c.153G>A) in the general population?

AK1 p.Ser51= (c.153G>A) is rare (popmax 0.834%, afr) (gnomAD).

AK1 p.Ser51=

Q: How is Hemolytic anemia due to adenylate kinase deficiency inherited?

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

c.153G>A · rs61741083 · VCV2059799

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.834%, afr)

Conditions

hemolytic anemia due to adenylate kinase deficiency

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 -13	GERP -4.9
Overall
CADD	2.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.834% African / African-American · 626/75,024 alleles

Filtering AF 0.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.759%

Overall 0.0504% 813/1,614,114 alleles · rare exomes 445/1,461,842 · genomes 368/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.834%	120
Middle Eastern	0.28%	357
Remaining individualsnot grpmax-eligible	0.0864%	1,158
Admixed American	0.0733%	1,364
South Asian	0.0132%	7,590
East Asian	0.00891%	11,220
European (non-Finnish)	0.00449%	22,264
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00313%	32,000

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: AK1
Protein: p.Ser51=
Coding: c.153G>A
MANE Select: NM_000476
dbSNP: rs61741083
Type: single nucleotide variant
Location: chr9:127872744 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.82 · 5 PDB
Residue 51: the 'nmp' region

Full AK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hemolytic anemia due to adenylate kinase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hemolytic anemia due to adenylate kinase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

AK1 p.Arg107Ter Pathogenic/Likely pathogenic ★★ same condition
AK1 p.Arg77Gln Uncertain significance ★★ ⚠ same condition
AK1 p.Arg77Trp Uncertain significance ★★ same condition
AK1 p.Glu26Asp Uncertain significance ★★ ⚠ same condition
AK1 p.Gly137Arg Uncertain significance ★★ ⚠ same condition
AK1 p.Gly177Asp Uncertain significance ★★ ⚠ same condition
AK1 p.Ile169Thr Uncertain significance ★★ same condition
AK1 p.Met80Val Uncertain significance ★★ ⚠ 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/ak1-p-ser51 (accessed [today's date]).

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