Is AK5 p.Arg155Gln (c.464G>A) pathogenic?

AK5 p.Arg155Gln (c.464G>A) is classified Uncertain significance in AK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1259); Ultra-rare (popmax 0.014%, nfe).

How common is AK5 p.Arg155Gln (c.464G>A) in the general population?

AK5 p.Arg155Gln (c.464G>A) is ultra-rare (popmax 0.014%, nfe) (gnomAD).

What do computational predictors say about AK5 p.Arg155Gln (c.464G>A)?

AlphaMissense predicts likely benign (score 0.1259) — an in-silico prediction, not a clinical call.

AK5 p.Arg155Gln

c.464G>A · VCV4260704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1259 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.014%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1259	likely benign
REVEL	0.581	indeterminate
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 276 kb · p 1.5e-10 · regional, not allelic
Overall
CADD	29.4	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 0.014% European (non-Finnish) · 165/1,179,804 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0105% 170/1,613,280 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.014%	7,150
African / African-American	0.00401%	24,961
East Asian	0.00223%	44,868
Remaining individualsnot grpmax-eligible	0.0016%	62,442

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: AK5
Protein: p.Arg155Gln
Coding: c.464G>A
MANE Select: NM_174858
Type: single nucleotide variant
Location: chr1:77297607 (GRCh38)
Gene constraint: LOEUF 0.5 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.51 · 1 PDB
Residue 155: the 'adenylate kinase 1' region

Full AK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AK5 p.Arg155Gly Uncertain significance ★ ⚠ same residue
AK5 c.1059+12C>T Benign ★★ same type
AK5 c.1621-3T>C Benign ★★ same type
AK5 p.Lys203= Benign ★★ same type
AK5 p.Arg412His Uncertain significance ★ ⚠ same type
AK5 p.Arg431Cys Uncertain significance ★ ⚠ same type
AK5 p.Arg431His Uncertain significance ★ ⚠ same type
AK5 p.Arg465Trp 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/ak5-p-arg155gln (accessed [today's date]).

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