Is ANKS6 p.Arg142Gln (c.425G>A) pathogenic?

ANKS6 p.Arg142Gln (c.425G>A) is classified Uncertain significance in ANKS6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-13). AlphaMissense: likely benign (0.132); Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with ANKS6 p.Arg142Gln (c.425G>A)?

ANKS6 p.Arg142Gln (c.425G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ANKS6 p.Arg142Gln (c.425G>A) in the general population?

ANKS6 p.Arg142Gln (c.425G>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about ANKS6 p.Arg142Gln (c.425G>A)?

AlphaMissense predicts likely benign (score 0.132) — an in-silico prediction, not a clinical call.

ANKS6 p.Arg142Gln

c.425G>A · rs764519360 · VCV2374569

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.132 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.132	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -5.03	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 7.6	GERP 1.6, 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

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 0.0178% East Asian · 8/44,862 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0116% 187/1,612,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,608
European (non-Finnish)	0.0141%	7,105
Admixed American	0.00833%	11,999
African / African-American	0.00534%	18,734
Remaining individualsnot grpmax-eligible	0.0032%	31,228
Finnishnot grpmax-eligible	0.00157%	63,648
South Asian	0.0011%	91,072

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.Arg142Gln
Coding: c.425G>A
MANE Select: NM_173551
dbSNP: rs764519360
Type: single nucleotide variant
Location: chr9:98790541 (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

Similar variants

ANKS6 p.Arg142Trp Uncertain significance ★★ ⚠ same residue
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.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-arg142gln (accessed [today's date]).

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