Is SALL4 p.Ser698= (c.2094C>T) pathogenic?

SALL4 p.Ser698= (c.2094C>T) is classified Likely benign in SALL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-16). Ultra-rare (popmax 0.0453%, afr); Associated with Duane-radial ray syndrome.

What condition is associated with SALL4 p.Ser698= (c.2094C>T)?

SALL4 p.Ser698= (c.2094C>T) is associated with Duane-radial ray syndrome (ClinVar).

How common is SALL4 p.Ser698= (c.2094C>T) in the general population?

SALL4 p.Ser698= (c.2094C>T) is ultra-rare (popmax 0.0453%, afr) (gnomAD).

SALL4 p.Ser698=

c.2094C>T · VCV3664648

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, afr)

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 2.1	GERP 0.32, phastCons 1
Overall
CADD	5.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0453% African / African-American · 34/75,010 alleles

Filtering AF 0.0333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0292%

Overall 0.0026% 42/1,614,086 alleles · ultra-rare exomes 24/1,461,850 · genomes 18/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0453%	2,206
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Admixed American	0.00333%	30,001
South Asian	0.0011%	91,088

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.Ser698=
Coding: c.2094C>T
MANE Select: NM_020436
Type: single nucleotide variant
Location: chr20:51790389 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.86 · 14 PDB
Residue 698: 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.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-ser698 (accessed [today's date]).

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