Is AUTS2 p.Pro367Ser (c.1099C>T) pathogenic?

AUTS2 p.Pro367Ser (c.1099C>T) is classified Uncertain significance in AUTS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-03). AlphaMissense: likely benign (0.0747); Very rare (popmax 0.000932%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AUTS2 p.Pro367Ser (c.1099C>T)?

AUTS2 p.Pro367Ser (c.1099C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AUTS2 p.Pro367Ser (c.1099C>T) in the general population?

AUTS2 p.Pro367Ser (c.1099C>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about AUTS2 p.Pro367Ser (c.1099C>T)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

AUTS2 p.Pro367Ser

c.1099C>T · VCV3668276

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -7.51	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 1.6	GERP 1.3, phastCons 0.88
Regional constraint	o/e 0.90	unconstrained · MANE · 1,165 kb · p 0.015 · regional, not allelic
Overall
CADD	23.7	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 0.000932% European (non-Finnish) · 11/1,179,984 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,960 alleles · very rare

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.Pro367Ser
Coding: c.1099C>T
MANE Select: NM_015570
Type: single nucleotide variant
Location: chr7:70763226 (GRCh38)
Gene constraint: LOEUF 0.232 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.89
Residue 367: the 'important for regulation of lamellipodia formation' region; the 'disordered' region

Full AUTS2 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

AUTS2 p.Pro367Arg Uncertain significance ★ ⚠ same residue
AUTS2 p.Pro367= Likely benign ★ same residue
AUTS2 c.1902+4C>T Uncertain significance ★★ same condition
AUTS2 p.Ala1215Thr Uncertain significance ★★ ⚠ same condition
AUTS2 p.Ala40Thr Uncertain significance ★★ ⚠ same condition
AUTS2 p.Arg1140Leu Uncertain significance ★★ ⚠ same condition
AUTS2 p.Arg1145Leu Uncertain significance ★★ ⚠ same condition
AUTS2 p.Arg1166Gly 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/auts2-p-pro367ser (accessed [today's date]).

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