Is SALL4 p.Pro504= (c.1512C>T) pathogenic?

SALL4 p.Pro504= (c.1512C>T) is classified Benign/Likely benign in SALL4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Rare (popmax 0.316%, sas); Associated with Duane-radial ray syndrome.

What condition is associated with SALL4 p.Pro504= (c.1512C>T)?

SALL4 p.Pro504= (c.1512C>T) is associated with Duane-radial ray syndrome (ClinVar).

How common is SALL4 p.Pro504= (c.1512C>T) in the general population?

SALL4 p.Pro504= (c.1512C>T) is rare (popmax 0.316%, sas) (gnomAD).

SALL4 p.Pro504=

c.1512C>T · rs138804604 · VCV2652413

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.316%, sas)

Conditions

Duane-radial ray syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 1.3, phastCons 1
Overall
CADD	6.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.316% South Asian · 288/91,086 alleles

Filtering AF 0.286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.274%

Overall 0.0389% 628/1,614,142 alleles · rare exomes 586/1,461,880 · genomes 42/152,262 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.316%	316
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0416%	2,404
European (non-Finnish)	0.0242%	4,126
African / African-American	0.0227%	4,414
Admixed American	0.00833%	12,005
East Asian	0.00223%	44,886
Finnishnot grpmax-eligible	0.00156%	64,012

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.Pro504=
Coding: c.1512C>T
MANE Select: NM_020436
dbSNP: rs138804604
Type: single nucleotide variant
Location: chr20:51790971 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.86 · 14 PDB
Residue 504: the 'disordered' region

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.Pro504Leu Uncertain significance ★ ⚠ 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
SALL4 p.Ala149Val 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-pro504 (accessed [today's date]).

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