Is ANKS6 p.Pro449= (c.1347C>T) pathogenic?

ANKS6 p.Pro449= (c.1347C>T) is classified Likely benign in ANKS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). Very rare (popmax 0.00659%, sas); Associated with nephronophthisis 16.

What condition is associated with ANKS6 p.Pro449= (c.1347C>T)?

ANKS6 p.Pro449= (c.1347C>T) is associated with nephronophthisis 16 (ClinVar).

How common is ANKS6 p.Pro449= (c.1347C>T) in the general population?

ANKS6 p.Pro449= (c.1347C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

How is Nephronophthisis inherited?

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

ANKS6 p.Pro449=

c.1347C>T · rs773417328 · VCV2161951

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

nephronophthisis 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -4.6
Overall
CADD	0.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,040 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00118% 19/1,613,900 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,173
African / African-American	0.00267%	37,466
European (non-Finnish)	0.000932%	107,277

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.Pro449=
Coding: c.1347C>T
MANE Select: NM_173551
dbSNP: rs773417328
Type: single nucleotide variant
Location: chr9:98780210 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.60 · 1 PDB

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-pro449 (accessed [today's date]).

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