Is SALL4 p.Pro147Ser (c.439C>T) pathogenic?

SALL4 p.Pro147Ser (c.439C>T) is classified Uncertain significance in SALL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: likely benign (0.0876); Absent from gnomAD v4.1; Associated with IVIC syndrome.

What condition is associated with SALL4 p.Pro147Ser (c.439C>T)?

SALL4 p.Pro147Ser (c.439C>T) is associated with IVIC syndrome, Duane-radial ray syndrome (ClinVar).

How common is SALL4 p.Pro147Ser (c.439C>T) in the general population?

SALL4 p.Pro147Ser (c.439C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SALL4 p.Pro147Ser (c.439C>T)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

SALL4 p.Pro147Ser

c.439C>T · VCV3587395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

IVIC syndrome

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -5.72	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 2.9	GERP 0.28, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,245 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	15.51	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

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.Pro147Ser
Coding: c.439C>T
MANE Select: NM_020436
Type: single nucleotide variant
Location: chr20:51792044 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.86 · 14 PDB
Residue 147: the 'disordered' region

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

Disease context

IVIC syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Duane-radial ray syndrome

Similar variants

SALL4 p.Pro147Leu Likely benign ★★ same residue
SALL4 p.Pro147= Likely benign ★ same residue
SALL4 p.Arg573Ter Pathogenic ★★ same condition
SALL4 p.Arg831Ter Pathogenic ★★ same condition
SALL4 p.Arg865Ter Pathogenic/Likely pathogenic ★★ same condition
SALL4 c.2743-3T>C Uncertain significance ★★ same condition
SALL4 p.Ala1004Val Uncertain significance ★★ ⚠ same condition
SALL4 p.Ala118Val 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/sall4-p-pro147ser (accessed [today's date]).

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