Is SALL4 p.Ser403= (c.1209C>T) pathogenic?

SALL4 p.Ser403= (c.1209C>T) is classified Likely benign in SALL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-05). Very rare (popmax 8.47e-05%, nfe); Associated with Duane-radial ray syndrome.

What condition is associated with SALL4 p.Ser403= (c.1209C>T)?

SALL4 p.Ser403= (c.1209C>T) is associated with Duane-radial ray syndrome (ClinVar).

How common is SALL4 p.Ser403= (c.1209C>T) in the general population?

SALL4 p.Ser403= (c.1209C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

SALL4 p.Ser403=

c.1209C>T · rs2078038422 · VCV1980092

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 2.6	GERP -0.83, phastCons 1
Overall
CADD	7.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.2e-05% 1/1,614,122 alleles · very rare exomes 1/1,461,824 · genomes 0/152,298 · 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.Ser403=
Coding: c.1209C>T
MANE Select: NM_020436
dbSNP: rs2078038422
Type: single nucleotide variant
Location: chr20:51791274 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.86 · 14 PDB
Residue 403: an α-helix

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-ser403 (accessed [today's date]).

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