Is ANKS6 p.Val65Phe (c.193G>T) pathogenic?

ANKS6 p.Val65Phe (c.193G>T) is classified Conflicting classifications of pathogenicity in ANKS6 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.12); Rare (popmax 0.316%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANKS6 p.Val65Phe (c.193G>T)?

ANKS6 p.Val65Phe (c.193G>T) is associated with Inborn genetic diseases, nephronophthisis 16 (ClinVar).

How common is ANKS6 p.Val65Phe (c.193G>T) in the general population?

ANKS6 p.Val65Phe (c.193G>T) is rare (popmax 0.316%, nfe) (gnomAD).

What do computational predictors say about ANKS6 p.Val65Phe (c.193G>T)?

AlphaMissense predicts likely benign (score 0.12) — an in-silico prediction, not a clinical call.

ANKS6 p.Val65Phe

c.193G>T · rs745881769 · VCV474447

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.12 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.316%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.12	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -9.48	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 0.46	GERP -0.79, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.79 · regional, not allelic
Overall
CADD	8.169	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 0.316% European (non-Finnish) · 3,178/1,004,342 alleles

Filtering AF 0.307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.303%

Overall 0.286% 3,610/1,264,420 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.503%	199
European (non-Finnish)grpmax	0.316%	316
South Asian	0.27%	370
Remaining individualsnot grpmax-eligible	0.223%	449
Middle Eastern	0.181%	554
Admixed American	0.0929%	1,077
African / African-American	0.0448%	2,232
East Asian	0.0256%	3,902

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val65Phe
Coding: c.193G>T
MANE Select: NM_173551
dbSNP: rs745881769
Type: single nucleotide variant
Location: chr9:98796299 (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 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-val65phe (accessed [today's date]).

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