Is AK3 p.Pro206Arg (c.617C>G) pathogenic?

AK3 p.Pro206Arg (c.617C>G) is classified Uncertain significance in AK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely pathogenic (0.6011); Rare (popmax 0.157%, sas).

How common is AK3 p.Pro206Arg (c.617C>G) in the general population?

AK3 p.Pro206Arg (c.617C>G) is rare (popmax 0.157%, sas) (gnomAD).

What do computational predictors say about AK3 p.Pro206Arg (c.617C>G)?

AlphaMissense predicts likely pathogenic (score 0.6011) — an in-silico prediction, not a clinical call.

AK3 p.Pro206Arg

c.617C>G · rs757819525 · VCV3103386

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6011 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.157%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6011	likely pathogenic
REVEL	0.627	indeterminate
SaProt	LLR -13.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.42	unconstrained · MANE · 28 kb · p 1.1e-12 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.157% South Asian · 143/91,020 alleles

Filtering AF 0.136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.00992% 160/1,613,362 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.157%	637
Remaining individualsnot grpmax-eligible	0.0256%	3,904
African / African-American	0.00134%	74,832

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: AK3
Protein: p.Pro206Arg
Coding: c.617C>G
MANE Select: NM_016282
dbSNP: rs757819525
Type: single nucleotide variant
Location: chr9:4713043 (GRCh38)
Gene constraint: LOEUF 1.602 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.79 · 4 PDB
Residue 206: an α-helix

Full AK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AK3 p.Ala223Ser Uncertain significance ★ ⚠ same type
AK3 p.Ala223Val Uncertain significance ★ ⚠ same type
AK3 p.Ala5Ser Uncertain significance ★ ⚠ same type
AK3 p.Ala75Thr Uncertain significance ★ ⚠ same type
AK3 p.Arg124Cys Uncertain significance ★ ⚠ same type
AK3 p.Arg128Gly Uncertain significance ★ ⚠ same type
AK3 p.Arg136Gln Uncertain significance ★ ⚠ same type
AK3 p.Arg161His 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/ak3-p-pro206arg (accessed [today's date]).

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