Is AGK p.Arg351Pro (c.1052G>C) pathogenic?

AGK p.Arg351Pro (c.1052G>C) is classified Likely benign in AGK (ClinVar, Single submitter, 1 submitter; last evaluated 2013-10-22). AlphaMissense: ambiguous (0.4292); Very rare (popmax 0.0022%, sas).

How common is AGK p.Arg351Pro (c.1052G>C) in the general population?

AGK p.Arg351Pro (c.1052G>C) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about AGK p.Arg351Pro (c.1052G>C)?

AlphaMissense predicts ambiguous (score 0.4292) — an in-silico prediction, not a clinical call.

AGK p.Arg351Pro

c.1052G>C · rs374861637 · VCV214063

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4292 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4292	ambiguous
REVEL	0.094	moderately benign-leaning
SaProt	LLR -13.05	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -0.37, phastCons 0.033
Overall
CADD	17.91	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000805% 13/1,614,088 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,543
African / African-American	0.00133%	74,928
European (non-Finnish)	0.000847%	118,003

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: AGK
Protein: p.Arg351Pro
Coding: c.1052G>C
MANE Select: NM_018238
dbSNP: rs374861637
Type: single nucleotide variant
Location: chr7:141651530 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.93 · 2 PDB
Residue 351: a UniProt-annotated variant site (in mtdps10)

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

Similar variants

AGK p.Arg351Gln Uncertain significance ★★ ⚠ same residue
AGK p.Arg351Ter Likely pathogenic ★ same residue
AGK c.1047-2A>T Pathogenic/Likely pathogenic ★★ same type
AGK c.222-2A>C Likely pathogenic ★★ same type
AGK c.297+2T>C Pathogenic ★★ same type
AGK c.424-3C>G Pathogenic/Likely pathogenic ★★ same type
AGK c.518+1G>A Pathogenic ★★ same type
AGK p.Arg137Ter Pathogenic ★★ 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/agk-p-arg351pro (accessed [today's date]).

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