Is ANKS6 p.Ala64Pro (c.190G>C) pathogenic?

ANKS6 p.Ala64Pro (c.190G>C) is classified Uncertain significance in ANKS6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-02-22). AlphaMissense: likely benign (0.071); Ultra-rare (popmax 0.0176%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANKS6 p.Ala64Pro (c.190G>C)?

ANKS6 p.Ala64Pro (c.190G>C) is associated with Inborn genetic diseases, nephronophthisis 16 (ClinVar).

How common is ANKS6 p.Ala64Pro (c.190G>C) in the general population?

ANKS6 p.Ala64Pro (c.190G>C) is ultra-rare (popmax 0.0176%, nfe) (gnomAD).

What do computational predictors say about ANKS6 p.Ala64Pro (c.190G>C)?

AlphaMissense predicts likely benign (score 0.071) — an in-silico prediction, not a clinical call.

ANKS6 p.Ala64Pro

c.190G>C · rs1022019420 · VCV1031714

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.071 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.071	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -6.70	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 -0.16	GERP -0.59, phastCons 0.94
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.79 · regional, not allelic
Overall
CADD	9.655	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% European (non-Finnish) · 177/1,003,320 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.0149% 188/1,262,436 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0176%	5,668
Admixed American	0.0112%	8,910
African / African-American	0.00775%	12,905
Remaining individualsnot grpmax-eligible	0.00645%	15,512

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.Ala64Pro
Coding: c.190G>C
MANE Select: NM_173551
dbSNP: rs1022019420
Type: single nucleotide variant
Location: chr9:98796302 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 16

Similar variants

ANKS6 p.Ala64fs Pathogenic ★ 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-ala64pro (accessed [today's date]).

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