Is AK2 c.93+153C>T pathogenic?

AK2 c.93+153C>T is classified Benign in AK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-10). Common (popmax 13.6%, mid) — too common for a highly-penetrant pathogenic allele.

AK2 c.93+153C>T

Q: How common is AK2 c.93+153C>T in the general population?

AK2 c.93+153C>T is common (popmax 13.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs11591185 · VCV1221575

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 13.6%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +153	deep intronic (+153 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	GERP -4.8
Non-coding constraint	Z 3.96	1 kb window · o/e 0.75 · regional · uncalibrated
Overall
CADD	4.872	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.6% Middle Eastern · 40/294 alleles

Filtering AF 12.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 12%

Overall 8.57% 13,044/152,150 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	14.9%	7
Middle Easterngrpmax	13.6%	7
European (non-Finnish)	12.3%	8
South Asian	11.1%	9
Ashkenazi Jewishnot grpmax-eligible	9.16%	11
Remaining individualsnot grpmax-eligible	8.72%	11
Admixed American	7.23%	14
Amishnot grpmax-eligible	5.81%	17
African / African-American	2.13%	47
East Asian	0.252%	397

Finnish 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: AK2
Coding: c.93+153C>T
MANE Select: NM_001625
dbSNP: rs11591185
Type: single nucleotide variant
Location: chr1:33036583 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.49 · 3 PDB

Full AK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AK2 c.330+5G>A Pathogenic ★★ same type
AK2 c.498+1G>A Pathogenic/Likely pathogenic ★★ same type
AK2 p.Ala182Asp Pathogenic/Likely pathogenic ★★ same type
AK2 p.Arg103Trp Pathogenic/Likely pathogenic ★★ same type
AK2 p.Arg175Pro Likely pathogenic ★★ same type
AK2 p.Met1Val Pathogenic ★★ same type
AK2 p.Ala212Thr Uncertain significance ★★ ⚠ same type
AK2 p.Ala2Val 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/ak2-c-93-plus-153c-t (accessed [today's date]).

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