Is AK3 p.Asp68Val (c.203A>T) pathogenic?

AK3 p.Asp68Val (c.203A>T) is classified Uncertain significance in AK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.9403); Ultra-rare (popmax 0.0626%, sas).

How common is AK3 p.Asp68Val (c.203A>T) in the general population?

AK3 p.Asp68Val (c.203A>T) is ultra-rare (popmax 0.0626%, sas) (gnomAD).

What do computational predictors say about AK3 p.Asp68Val (c.203A>T)?

AlphaMissense predicts likely pathogenic (score 0.9403) — an in-silico prediction, not a clinical call.

AK3 p.Asp68Val

c.203A>T · rs141767297 · VCV2357165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9403 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9403	likely pathogenic
REVEL	0.947	strongly pathogenic-leaning
SaProt	LLR -13.38	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 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 1.42	unconstrained · MANE · 28 kb · p 1.1e-12 · 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

Grpmax group 0.0626% South Asian · 57/91,088 alleles

Filtering AF 0.0496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0449%

Overall 0.0111% 179/1,614,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0626%	1,598
Middle Eastern	0.0329%	3,042
Admixed American	0.015%	6,668
Remaining individualsnot grpmax-eligible	0.0144%	6,943
European (non-Finnish)	0.00864%	11,569

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.Asp68Val
Coding: c.203A>T
MANE Select: NM_016282
dbSNP: rs141767297
Type: single nucleotide variant
Location: chr9:4722574 (GRCh38)
Gene constraint: LOEUF 1.602 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.79 · 4 PDB
Residue 68: 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-asp68val (accessed [today's date]).

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