Is ANKS6 p.Ser647= (c.1941C>T) pathogenic?

ANKS6 p.Ser647= (c.1941C>T) is classified Likely benign in ANKS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). Ultra-rare (popmax 0.0189%, eas); Associated with nephronophthisis 16.

What condition is associated with ANKS6 p.Ser647= (c.1941C>T)?

ANKS6 p.Ser647= (c.1941C>T) is associated with nephronophthisis 16 (ClinVar).

How common is ANKS6 p.Ser647= (c.1941C>T) in the general population?

ANKS6 p.Ser647= (c.1941C>T) is ultra-rare (popmax 0.0189%, eas) (gnomAD).

How is Nephronophthisis inherited?

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

ANKS6 p.Ser647=

c.1941C>T · VCV4693316

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0189%, eas)

Conditions

nephronophthisis 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.157	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.57, phastCons 1
Overall
CADD	4.692	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0189% East Asian · 8/42,424 alleles

Filtering AF 0.00938% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00683%

Overall 0.00146% 23/1,570,560 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0189%	5,303
Remaining individualsnot grpmax-eligible	0.0099%	10,101
European (non-Finnish)	0.000778%	128,595

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.Ser647=
Coding: c.1941C>T
MANE Select: NM_173551
Type: single nucleotide variant
Location: chr9:98770927 (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 647: 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.Ser647Asn Uncertain significance ★★ ⚠ same residue
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

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-ser647 (accessed [today's date]).

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