Is AUTS2 p.Pro63Gln (c.188C>A) pathogenic?

AUTS2 p.Pro63Gln (c.188C>A) is classified Likely benign in AUTS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1094); Rare (popmax 0.606%, eas); Associated with autism spectrum disorder due to AUTS2 deficiency.

What condition is associated with AUTS2 p.Pro63Gln (c.188C>A)?

AUTS2 p.Pro63Gln (c.188C>A) is associated with autism spectrum disorder due to AUTS2 deficiency (ClinVar).

How common is AUTS2 p.Pro63Gln (c.188C>A) in the general population?

AUTS2 p.Pro63Gln (c.188C>A) is rare (popmax 0.606%, eas) (gnomAD).

How is Autism spectrum disorder due to AUTS2 deficiency inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about AUTS2 p.Pro63Gln (c.188C>A)?

AlphaMissense predicts likely benign (score 0.1094) — an in-silico prediction, not a clinical call.

AUTS2 p.Pro63Gln

c.188C>A · rs199945820 · VCV702447

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1094 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.606%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autism spectrum disorder due to AUTS2 deficiency

Computational evidence

Protein change
AlphaMissense	0.1094	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.92	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 4.5	GERP 0.96, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 1,165 kb · p 0.015 · regional, not allelic
Overall
CADD	25.3	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 0.606% East Asian · 271/44,706 alleles

Filtering AF 0.547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.524%

Overall 0.0174% 281/1,612,054 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.606%	165
Remaining individualsnot grpmax-eligible	0.00801%	12,483
South Asian	0.0022%	45,517
Admixed American	0.00167%	59,948
European (non-Finnish)	0.00017%	589,703

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: AUTS2
Protein: p.Pro63Gln
Coding: c.188C>A
MANE Select: NM_015570
dbSNP: rs199945820
Type: single nucleotide variant
Location: chr7:69599841 (GRCh38)
Gene constraint: LOEUF 0.232 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.89
Residue 63: the 'disordered' region

Full AUTS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autism spectrum disorder due to AUTS2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autism spectrum disorder due to AUTS2 deficiency (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

AUTS2 p.Pro63Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
AUTS2 p.Pro63= Likely benign ★ same residue
AUTS2 c.2005-1G>C Likely pathogenic ★★ same condition
AUTS2 c.742+1G>A Pathogenic ★★ same condition
AUTS2 p.Arg126Ter Pathogenic/Likely pathogenic ★★ same condition
AUTS2 p.Arg152Ter Pathogenic/Likely pathogenic ★★ same condition
AUTS2 p.Arg316Ter Pathogenic/Likely pathogenic ★★ same condition
AUTS2 p.Arg495Ter Pathogenic ★★ 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/auts2-p-pro63gln (accessed [today's date]).

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