Is SALL4 p.Pro565Ser (c.1693C>T) pathogenic?

SALL4 p.Pro565Ser (c.1693C>T) is classified Uncertain significance in SALL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-11). AlphaMissense: ambiguous (0.3483); Absent from gnomAD v4.1; Associated with SALL4-Related Disorders.

What condition is associated with SALL4 p.Pro565Ser (c.1693C>T)?

SALL4 p.Pro565Ser (c.1693C>T) is associated with SALL4-Related Disorders (ClinVar).

How common is SALL4 p.Pro565Ser (c.1693C>T) in the general population?

SALL4 p.Pro565Ser (c.1693C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SALL4 p.Pro565Ser (c.1693C>T)?

AlphaMissense predicts ambiguous (score 0.3483) — an in-silico prediction, not a clinical call.

SALL4 p.Pro565Ser

c.1693C>T · rs2078032654 · VCV2498217

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3483 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

SALL4-Related Disorders

Computational evidence

Protein change
AlphaMissense	0.3483	ambiguous
REVEL	0.315	indeterminate
SaProt	LLR -5.33	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,245 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	24.8	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

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: SALL4
Protein: p.Pro565Ser
Coding: c.1693C>T
MANE Select: NM_020436
dbSNP: rs2078032654
Type: single nucleotide variant
Location: chr20:51790790 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.86 · 14 PDB

Full SALL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SALL4-Related Disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SALL4 p.Gly406Glu Uncertain significance ★★ ⚠ same condition
SALL4 p.Thr179Ser Uncertain significance ★★ ⚠ same condition
SALL4 p.Ala56Val Conflicting classifications of pathogenicity ★ ⚠ same condition
SALL4 p.Arg865Leu Uncertain significance ★ ⚠ same condition
SALL4 p.His296Gln Uncertain significance ★ ⚠ same condition
SALL4 p.Pro23Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
SALL4 p.Ser388Cys Uncertain significance ★ ⚠ same condition
SALL4 p.Thr256Ala Conflicting classifications of pathogenicity ★ ⚠ 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/sall4-p-pro565ser (accessed [today's date]).

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