Is AK3 p.Ala5Ser (c.13G>T) pathogenic?

AK3 p.Ala5Ser (c.13G>T) is classified Uncertain significance in AK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.0788); Ultra-rare (popmax 0.0262%, nfe).

How common is AK3 p.Ala5Ser (c.13G>T) in the general population?

AK3 p.Ala5Ser (c.13G>T) is ultra-rare (popmax 0.0262%, nfe) (gnomAD).

What do computational predictors say about AK3 p.Ala5Ser (c.13G>T)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

AK3 p.Ala5Ser

c.13G>T · rs201009389 · VCV2403160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0262%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -4.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -3.1, phastCons 0.004
Regional constraint	o/e 1.42	unconstrained · MANE · 28 kb · p 1.1e-12 · regional, not allelic
Overall
CADD	16.42	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0262% European (non-Finnish) · 301/1,148,126 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0228%

Overall 0.0207% 320/1,545,804 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0262%	3,814
Remaining individualsnot grpmax-eligible	0.0167%	5,983
African / African-American	0.00706%	14,155
Finnishnot grpmax-eligible	0.00496%	20,149
Admixed American	0.002%	49,962

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.Ala5Ser
Coding: c.13G>T
MANE Select: NM_016282
dbSNP: rs201009389
Type: single nucleotide variant
Location: chr9:4741075 (GRCh38)
Gene constraint: LOEUF 1.602 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.79 · 4 PDB

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.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
AK3 p.Arg161Leu 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-ala5ser (accessed [today's date]).

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