Is AGK p.Pro324Leu (c.971C>T) pathogenic?

AGK p.Pro324Leu (c.971C>T) is classified Conflicting classifications of pathogenicity in AGK (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-07-03). AlphaMissense: likely benign (0.0573); Ultra-rare (popmax 0.0499%, mid); Associated with Inborn genetic diseases.

What condition is associated with AGK p.Pro324Leu (c.971C>T)?

AGK p.Pro324Leu (c.971C>T) is associated with Inborn genetic diseases, Sengers syndrome, cataract 38 (ClinVar).

How common is AGK p.Pro324Leu (c.971C>T) in the general population?

AGK p.Pro324Leu (c.971C>T) is ultra-rare (popmax 0.0499%, mid) (gnomAD).

What do computational predictors say about AGK p.Pro324Leu (c.971C>T)?

AlphaMissense predicts likely benign (score 0.0573) — an in-silico prediction, not a clinical call.

AGK p.Pro324Leu

c.971C>T · rs553909597 · VCV2045930

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0573 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0499%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0573	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -5.71	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 0.058	GERP 3.5, phastCons 0.41
Overall
CADD	3.232	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 0.0499% Middle Eastern · 3/6,016 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00723%

Overall 0.00152% 24/1,574,722 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0499%	2,005
African / African-American	0.0134%	7,454
East Asian	0.0115%	8,720
South Asian	0.00234%	42,816
Admixed American	0.00186%	53,786
European (non-Finnish)	0.000259%	386,297

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.Pro324Leu
Coding: c.971C>T
MANE Select: NM_018238
dbSNP: rs553909597
Type: single nucleotide variant
Location: chr7:141641904 (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 324: a UniProt-annotated variant site (in mtdps10)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Sengers syndrome cataract 38

Similar variants

AGK p.Pro324= Likely benign ★ same residue
AGK c.1047-2A>T Pathogenic/Likely pathogenic ★★ same condition
AGK c.222-2A>C Likely pathogenic ★★ same condition
AGK c.297+2T>C Pathogenic ★★ same condition
AGK c.424-3C>G Pathogenic/Likely pathogenic ★★ same condition
AGK c.518+1G>A Pathogenic ★★ same condition
AGK p.Arg137Ter Pathogenic ★★ same condition
AGK p.Arg138Ter Pathogenic ★★ same condition

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-pro324leu (accessed [today's date]).

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