Is SALL4 p.Ser285Pro (c.853T>C) pathogenic?

SALL4 p.Ser285Pro (c.853T>C) is classified Uncertain significance in SALL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely benign (0.0826); Very rare (popmax 0.00167%, amr); Associated with Duane-radial ray syndrome.

What condition is associated with SALL4 p.Ser285Pro (c.853T>C)?

SALL4 p.Ser285Pro (c.853T>C) is associated with Duane-radial ray syndrome (ClinVar).

How common is SALL4 p.Ser285Pro (c.853T>C) in the general population?

SALL4 p.Ser285Pro (c.853T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about SALL4 p.Ser285Pro (c.853T>C)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

SALL4 p.Ser285Pro

c.853T>C · rs2078043324 · VCV1988477

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Duane-radial ray syndrome

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -6.46	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 2.5	GERP -4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,245 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	16.02	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 0.00167% Admixed American · 1/60,010 alleles

Overall 6.2e-05% 1/1,613,846 alleles · very rare exomes 0/1,461,620 · genomes 1/152,226 · joint denominator

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: SALL4
Protein: p.Ser285Pro
Coding: c.853T>C
MANE Select: NM_020436
dbSNP: rs2078043324
Type: single nucleotide variant
Location: chr20:51791630 (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

Duane-radial ray syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
SALL4 p.Ala149Val Uncertain significance ★★ ⚠ same condition
SALL4 p.Ala192Glu 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-ser285pro (accessed [today's date]).

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