Is ANKS6 p.Val644Ile (c.1930G>A) pathogenic?

ANKS6 p.Val644Ile (c.1930G>A) is classified Benign in ANKS6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0787); Common (popmax 96.9%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with nephronophthisis 16.

What condition is associated with ANKS6 p.Val644Ile (c.1930G>A)?

ANKS6 p.Val644Ile (c.1930G>A) is associated with nephronophthisis 16 (ClinVar).

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.Val644Ile (c.1930G>A)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

ANKS6 p.Val644Ile

Q: How common is ANKS6 p.Val644Ile (c.1930G>A) in the general population?

ANKS6 p.Val644Ile (c.1930G>A) is common (popmax 96.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1930G>A · rs6415847 · VCV262847

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 96.9%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis 16

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.69	GERP 2.5, phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.79 · regional, not allelic
Overall
CADD	2.412	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 96.9% European (non-Finnish) · 1,129,577/1,165,924 alleles

Filtering AF 96.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 96.7%

Overall 95.2% 1,510,007/1,586,358 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	99.9%	1
Finnishnot grpmax-eligible	99.1%	1
European (non-Finnish)grpmax	96.9%	1
African / African-American	95.4%	1
Middle Eastern	95.4%	1
Ashkenazi Jewishnot grpmax-eligible	94.8%	1
Remaining individualsnot grpmax-eligible	94.7%	1
South Asian	88.5%	1
Admixed American	83.2%	1
East Asian	73.1%	1

Amish 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.Val644Ile
Coding: c.1930G>A
MANE Select: NM_173551
dbSNP: rs6415847
Type: single nucleotide variant
Location: chr9:98770938 (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 644: the 'disordered' region; a UniProt-annotated variant site (in)

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-val644ile (accessed [today's date]).

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