Is ANKS6 p.Glu44fs (c.130_157del) pathogenic?

ANKS6 p.Glu44fs (c.130157del) is classified Pathogenic in ANKS6 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-06-30). Very rare (popmax 0.00186%, nfe); Associated with nephronophthisis 16.

What condition is associated with ANKS6 p.Glu44fs (c.130_157del)?

ANKS6 p.Glu44fs (c.130_157del) is associated with nephronophthisis 16 (ClinVar).

How common is ANKS6 p.Glu44fs (c.130_157del) in the general population?

ANKS6 p.Glu44fs (c.130_157del) is very rare (popmax 0.00186%, nfe) (gnomAD).

How is Nephronophthisis inherited?

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

ANKS6 p.Glu44fs

c.130_157del · rs1564236717 · VCV591737

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Conditions

nephronophthisis 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP 0.99, phastCons 1
Region caveats
Repeat context	tandem	(CGGCCC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 18/966,674 alleles

Filtering AF 0.00116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00096%

Overall 0.00181% 19/1,047,440 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00233%	42,920
European (non-Finnish)grpmax	0.00186%	53,704

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ANKS6
Protein: p.Glu44fs
Coding: c.130_157del
MANE Select: NM_173551
dbSNP: rs1564236717
Type: Deletion
Location: chr9:98796335 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.60 · 1 PDB
Residue 44: the 'disordered' region

Full ANKS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

ANKS6 p.Glu44Ala Uncertain significance ★ ⚠ same residue
ANKS6 p.Glu44_Pro49del Uncertain significance ★ same residue
ANKS6 p.Asp288fs Pathogenic/Likely pathogenic ★★ same condition
ANKS6 p.Tyr790_Gln791delinsTer Pathogenic ★★ same condition
ANKS6 c.2327-19del Benign/Likely benign ★★ same condition
ANKS6 p.Ala145fs Pathogenic ★ same condition
ANKS6 p.Ala52fs Pathogenic ★ same condition
ANKS6 p.Ala64fs 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/anks6-p-glu44fs (accessed [today's date]).

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