Is ANKS6 p.Ser769Arg (c.2305A>C) pathogenic?

ANKS6 p.Ser769Arg (c.2305A>C) is classified Uncertain significance in ANKS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). AlphaMissense: likely pathogenic (0.9881); Very rare (popmax 0.00401%, afr); Associated with Inborn genetic diseases.

What condition is associated with ANKS6 p.Ser769Arg (c.2305A>C)?

ANKS6 p.Ser769Arg (c.2305A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ANKS6 p.Ser769Arg (c.2305A>C) in the general population?

ANKS6 p.Ser769Arg (c.2305A>C) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about ANKS6 p.Ser769Arg (c.2305A>C)?

AlphaMissense predicts likely pathogenic (score 0.9881) — an in-silico prediction, not a clinical call.

ANKS6 p.Ser769Arg

c.2305A>C · VCV3400122

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9881 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9881	likely pathogenic · top 3% in ANKS6
REVEL	0.51	indeterminate
SaProt	LLR -8.11	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 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.79 · regional, not allelic
Overall
CADD	25.8	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 0.00401% African / African-American · 3/74,864 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00031% 5/1,613,350 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,955
Remaining individualsnot grpmax-eligible	0.0032%	31,226

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.Ser769Arg
Coding: c.2305A>C
MANE Select: NM_173551
Type: single nucleotide variant
Location: chr9:98756441 (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 769: the 'disordered' region

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

Similar variants

ANKS6 p.Ala363Val Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala589Glu Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala64Pro Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala835Thr Uncertain significance ★★ ⚠ same condition
ANKS6 p.Ala9Val Uncertain significance ★★ ⚠ same condition
ANKS6 p.Arg142Gln Uncertain significance ★★ ⚠ same condition
ANKS6 p.Arg153Trp Uncertain significance ★★ same condition
ANKS6 p.Arg427Trp 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-ser769arg (accessed [today's date]).

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