Is SASH1 p.Ser522Arg (c.1564A>C) pathogenic?

SASH1 p.Ser522Arg (c.1564A>C) is classified Likely pathogenic in SASH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1; Associated with SASH1-related disorder.

What condition is associated with SASH1 p.Ser522Arg (c.1564A>C)?

SASH1 p.Ser522Arg (c.1564A>C) is associated with SASH1-related disorder (ClinVar).

How common is SASH1 p.Ser522Arg (c.1564A>C) in the general population?

SASH1 p.Ser522Arg (c.1564A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SASH1 p.Ser522Arg (c.1564A>C)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

SASH1 p.Ser522Arg

c.1564A>C · VCV4894334

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

SASH1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic ✓ concordant with ClinVar · top 3% in SASH1
REVEL	0.514	indeterminate
SaProt	LLR -11.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 13 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SASH1
Protein: p.Ser522Arg
Coding: c.1564A>C
MANE Select: NM_015278
Type: single nucleotide variant
Location: chr6:148531661 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.90 · 2 PDB
Residue 522: the 'disordered' region

Full SASH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SASH1-related disorder

Similar variants

SASH1 p.Ser522= Likely benign ★ same residue
SASH1 p.Ile440Thr Uncertain significance ⚠ same condition
SASH1 c.1209+436G>A Benign same condition
SASH1 c.428-4T>G Likely benign same condition
SASH1 p.Gly309= Likely benign same condition
SASH1 p.Gly398Arg Likely benign same condition
SASH1 p.Ile1228Val Likely benign same condition
SASH1 p.Thr1167= Likely benign 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/sash1-p-ser522arg (accessed [today's date]).

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