Is ANKS6 p.Ser709= (c.2127C>T) pathogenic?

ANKS6 p.Ser709= (c.2127C>T) is classified Benign in ANKS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-10). Rare (popmax 0.21%, sas); Associated with nephronophthisis 16.

What condition is associated with ANKS6 p.Ser709= (c.2127C>T)?

ANKS6 p.Ser709= (c.2127C>T) is associated with nephronophthisis 16 (ClinVar).

How common is ANKS6 p.Ser709= (c.2127C>T) in the general population?

ANKS6 p.Ser709= (c.2127C>T) is rare (popmax 0.21%, sas) (gnomAD).

How is Nephronophthisis inherited?

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

ANKS6 p.Ser709=

c.2127C>T · rs553135386 · VCV2715297

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.21%, sas)

Conditions

nephronophthisis 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.01	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.73	GERP -2.4
Overall
CADD	2.774	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.21% South Asian · 190/90,510 alleles

Filtering AF 0.185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.176%

Overall 0.0147% 237/1,609,852 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.21%	476
Middle Eastern	0.0191%	5,246
Remaining individualsnot grpmax-eligible	0.0128%	7,791
Admixed American	0.00672%	14,885
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,478
European (non-Finnish)	0.00263%	38,015
East Asian	0.00223%	44,844
African / African-American	0.00133%	74,998

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.Ser709=
Coding: c.2127C>T
MANE Select: NM_173551
dbSNP: rs553135386
Type: single nucleotide variant
Location: chr9:98768096 (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 709: 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 c.1973-3C>G Pathogenic/Likely pathogenic ★★ same condition
ANKS6 p.Arg461Ter Pathogenic/Likely pathogenic ★★ same condition
ANKS6 c.907+6C>T Uncertain significance ★★ same condition
ANKS6 p.Ala215Thr Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala215Val Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala249Thr Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala261Thr Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala350Thr Uncertain significance ★★ ⚠ 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-ser709 (accessed [today's date]).

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