Is AK2 p.Arg103Pro (c.308G>C) pathogenic?

AK2 p.Arg103Pro (c.308G>C) is classified Uncertain significance in AK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-24). AlphaMissense: likely pathogenic (0.9941); Absent from gnomAD v4.1.

How common is AK2 p.Arg103Pro (c.308G>C) in the general population?

AK2 p.Arg103Pro (c.308G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AK2 p.Arg103Pro (c.308G>C)?

AlphaMissense predicts likely pathogenic (score 0.9941) — an in-silico prediction, not a clinical call.

AK2 p.Arg103Pro

c.308G>C · rs762416285 · VCV1677974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9941	likely pathogenic · top 7% in AK2
REVEL	0.817	moderately pathogenic-leaning
SaProt	LLR -17.02	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 24 kb · p 0.0069 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AK2
Protein: p.Arg103Pro
Coding: c.308G>C
MANE Select: NM_001625
dbSNP: rs762416285
Type: single nucleotide variant
Location: chr1:33021615 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.49 · 3 PDB
Residue 103: a binding site; a UniProt-annotated variant site (in rdys)

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

Similar variants

AK2 p.Arg103Trp Pathogenic/Likely pathogenic ★★ same residue
AK2 p.Arg103= Likely benign ★★ same residue
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.Arg175Pro Likely pathogenic ★★ same type
AK2 p.Met1Val Pathogenic ★★ same type
AK2 p.Ala212Thr 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-p-arg103pro (accessed [today's date]).

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