Is ANKS6 p.Met230Ile (c.690G>A) pathogenic?

ANKS6 p.Met230Ile (c.690G>A) is classified Uncertain significance in ANKS6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-04). AlphaMissense: likely pathogenic (0.8455); Rare (popmax 0.679%, mid); Associated with Inborn genetic diseases.

What condition is associated with ANKS6 p.Met230Ile (c.690G>A)?

ANKS6 p.Met230Ile (c.690G>A) is associated with Inborn genetic diseases, nephronophthisis 16 (ClinVar).

How common is ANKS6 p.Met230Ile (c.690G>A) in the general population?

ANKS6 p.Met230Ile (c.690G>A) is rare (popmax 0.679%, mid) (gnomAD).

What do computational predictors say about ANKS6 p.Met230Ile (c.690G>A)?

AlphaMissense predicts likely pathogenic (score 0.8455) — an in-silico prediction, not a clinical call.

ANKS6 p.Met230Ile

c.690G>A · rs201704559 · VCV1486559

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8455 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.679%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8455	likely pathogenic
REVEL	0.402	indeterminate
SaProt	LLR -7.69	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.79 · regional, not allelic
Overall
CADD	26.0	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 0.679% Middle Eastern · 41/6,042 alleles

Filtering AF 0.514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.457%

Overall 0.00542% 87/1,604,116 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.679%	147
Remaining individualsnot grpmax-eligible	0.0242%	4,135
South Asian	0.0154%	6,491
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,496
European (non-Finnish)	0.00136%	73,340

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.Met230Ile
Coding: c.690G>A
MANE Select: NM_173551
dbSNP: rs201704559
Type: single nucleotide variant
Location: chr9:98790276 (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-met230ile (accessed [today's date]).

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