Is ANKS6 p.Tyr378= (c.1134T>C) pathogenic?

ANKS6 p.Tyr378= (c.1134T>C) is classified Likely benign in ANKS6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.033%, mid); Associated with nephronophthisis 16.

What condition is associated with ANKS6 p.Tyr378= (c.1134T>C)?

ANKS6 p.Tyr378= (c.1134T>C) is associated with nephronophthisis 16 (ClinVar).

How common is ANKS6 p.Tyr378= (c.1134T>C) in the general population?

ANKS6 p.Tyr378= (c.1134T>C) is ultra-rare (popmax 0.033%, mid) (gnomAD).

How is Nephronophthisis inherited?

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

ANKS6 p.Tyr378=

c.1134T>C · rs200656157 · VCV262838

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 -0.31	GERP -4.3, phastCons 0.001
Overall
CADD	0.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00844%

Overall 0.00911% 147/1,614,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,701
European (non-Finnish)	0.0106%	9,440
Admixed American	0.00833%	12,004
Remaining individualsnot grpmax-eligible	0.008%	12,501
African / African-American	0.00266%	37,532

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.Tyr378=
Coding: c.1134T>C
MANE Select: NM_173551
dbSNP: rs200656157
Type: single nucleotide variant
Location: chr9:98782552 (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 p.Tyr378Cys 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-tyr378 (accessed [today's date]).

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