Is AK1 p.Pro96= (c.288G>A) pathogenic?

AK1 p.Pro96= (c.288G>A) is classified Likely benign in AK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-27). Very rare (popmax 0.005%, amr).

How common is AK1 p.Pro96= (c.288G>A) in the general population?

AK1 p.Pro96= (c.288G>A) is very rare (popmax 0.005%, amr) (gnomAD).

AK1 p.Pro96=

c.288G>A · rs931317223 · VCV1626397

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.123	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.7	GERP -4.7
Overall
CADD	0.444	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00397% 64/1,614,032 alleles · very rare exomes 60/1,461,866 · genomes 4/152,166 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0208%	4,807
Admixed Americangrpmax	0.005%	20,000
East Asian	0.00445%	22,450
European (non-Finnish)	0.00381%	26,223
South Asian	0.0011%	91,084

Remaining individuals 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: AK1
Protein: p.Pro96=
Coding: c.288G>A
MANE Select: NM_000476
dbSNP: rs931317223
Type: single nucleotide variant
Location: chr9:127871859 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.82 · 5 PDB
Residue 96: a binding site

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

Similar variants

AK1 p.Pro96Leu Uncertain significance ★ ⚠ same residue
AK1 p.Arg107Ter Pathogenic/Likely pathogenic ★★ same type
AK1 p.Arg77Gln Uncertain significance ★★ ⚠ same type
AK1 p.Arg77Trp Uncertain significance ★★ same type
AK1 p.Glu26Asp Uncertain significance ★★ ⚠ same type
AK1 p.Gly137Arg Uncertain significance ★★ ⚠ same type
AK1 p.Gly177Asp Uncertain significance ★★ ⚠ same type
AK1 p.Ile169Thr 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/ak1-p-pro96 (accessed [today's date]).

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