Is AGK c.101+7A>C pathogenic?

AGK c.101+7A>C is classified Conflicting classifications of pathogenicity in AGK (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-28). Very rare (popmax 0.0029%, nfe); Associated with Sengers syndrome.

What condition is associated with AGK c.101+7A>C?

AGK c.101+7A>C is associated with Sengers syndrome, cataract 38 (ClinVar).

How common is AGK c.101+7A>C in the general population?

AGK c.101+7A>C is very rare (popmax 0.0029%, nfe) (gnomAD).

AGK c.101+7A>C

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.

rs373899577 · VCV1175770

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0029%, nfe)

Conditions

Sengers syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +7	near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone
SpliceAI	Δ0.23	donor loss · deltas
Constraint at this position
Conservation	phyloP 0.31	GERP 3.7
Non-coding constraint	Z 4.21	1 kb window · o/e 0.70 · regional · uncalibrated
Overall
CADD	11.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0029% European (non-Finnish) · 34/1,173,814 alleles

Filtering AF 0.00209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00184%

Overall 0.00212% 34/1,605,976 alleles · very rare

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+7A>C
MANE Select: NM_018238
dbSNP: rs373899577
Type: single nucleotide variant
Location: chr7:141555574 (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-7a-c (accessed [today's date]).

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