Is AGK c.101+5C>T pathogenic?

AGK c.101+5C>T is classified Benign/Likely benign in AGK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-03-01). Low-frequency (popmax 1.09%, afr); Associated with Sengers syndrome.

What condition is associated with AGK c.101+5C>T?

AGK c.101+5C>T is associated with Sengers syndrome, cataract 38 (ClinVar).

How common is AGK c.101+5C>T in the general population?

AGK c.101+5C>T is low-frequency (popmax 1.09%, afr) (gnomAD).

AGK c.101+5C>T

Q: How is Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

rs150421355 · VCV136318

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.09%, afr)

Conditions

Sengers syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.8	GERP -6
Non-coding constraint	Z 4.21	1 kb window · o/e 0.70 · regional · uncalibrated
Overall
CADD	0.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.09% African / African-American · 813/74,832 alleles

Filtering AF 1.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 1%

Overall 0.0554% 891/1,606,982 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.09%	92
Remaining individualsnot grpmax-eligible	0.0739%	1,354
Admixed American	0.0469%	2,132
Middle Eastern	0.0166%	6,036
South Asian	0.00221%	45,240
European (non-Finnish)	8.51e-05%	1,174,475

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
Coding: c.101+5C>T
MANE Select: NM_018238
dbSNP: rs150421355
Type: single nucleotide variant
Location: chr7:141555572 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.93 · 2 PDB

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

Disease context

Sengers syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cataract 38

For Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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
AGK p.Arg281Ter 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-c-101-plus-5c-t (accessed [today's date]).

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