Is ANKS6 p.Ala515Val (c.1544C>T) pathogenic?

ANKS6 p.Ala515Val (c.1544C>T) is classified Conflicting classifications of pathogenicity in ANKS6 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-06-02). AlphaMissense: likely benign (0.0646); Very rare (popmax 0.00729%, nfe); Associated with nephronophthisis 16.

What condition is associated with ANKS6 p.Ala515Val (c.1544C>T)?

ANKS6 p.Ala515Val (c.1544C>T) is associated with nephronophthisis 16 (ClinVar).

How common is ANKS6 p.Ala515Val (c.1544C>T) in the general population?

ANKS6 p.Ala515Val (c.1544C>T) is very rare (popmax 0.00729%, nfe) (gnomAD).

How is Nephronophthisis inherited?

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

What do computational predictors say about ANKS6 p.Ala515Val (c.1544C>T)?

AlphaMissense predicts likely benign (score 0.0646) — an in-silico prediction, not a clinical call.

ANKS6 p.Ala515Val

c.1544C>T · rs141766991 · VCV2328622

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0646 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis 16

Computational evidence

Protein change
AlphaMissense	0.0646	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -4.3
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.79 · regional, not allelic
Overall
CADD	0.278	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00729% European (non-Finnish) · 86/1,180,034 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00558% 90/1,614,164 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00729%	13,721
South Asian	0.00329%	30,355
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Ala515Val
Coding: c.1544C>T
MANE Select: NM_173551
dbSNP: rs141766991
Type: single nucleotide variant
Location: chr9:98778249 (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 515: 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.Ala515= Likely benign ★ 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-ala515val (accessed [today's date]).

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