Is SALL4 p.Pro339= (c.1017G>A) pathogenic?

SALL4 p.Pro339= (c.1017G>A) is classified Likely benign in SALL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-25). Ultra-rare (popmax 0.0468%, eas); Associated with Duane-radial ray syndrome.

What condition is associated with SALL4 p.Pro339= (c.1017G>A)?

SALL4 p.Pro339= (c.1017G>A) is associated with Duane-radial ray syndrome (ClinVar).

How common is SALL4 p.Pro339= (c.1017G>A) in the general population?

SALL4 p.Pro339= (c.1017G>A) is ultra-rare (popmax 0.0468%, eas) (gnomAD).

SALL4 p.Pro339=

c.1017G>A · VCV4744512

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, eas)

Conditions

Duane-radial ray syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -4.7
Overall
CADD	0.312	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0468% East Asian · 21/44,886 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0263%

Overall 0.00917% 148/1,613,998 alleles · ultra-rare exomes 137/1,461,812 · genomes 11/152,186 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0468%	2,137
European (non-Finnish)	0.01%	10,000
African / African-American	0.00667%	14,983
Admixed American	0.00333%	30,007
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Pro339=
Coding: c.1017G>A
MANE Select: NM_020436
Type: single nucleotide variant
Location: chr20:51791466 (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-pro339 (accessed [today's date]).

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