Is SALL4 p.Ala352= (c.1056G>A) pathogenic?

SALL4 p.Ala352= (c.1056G>A) is classified Benign in SALL4 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-01). Common (popmax 32.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with IVIC syndrome.

What condition is associated with SALL4 p.Ala352= (c.1056G>A)?

SALL4 p.Ala352= (c.1056G>A) is associated with IVIC syndrome, Duane-radial ray syndrome (ClinVar).

SALL4 p.Ala352=

Q: How common is SALL4 p.Ala352= (c.1056G>A) in the general population?

SALL4 p.Ala352= (c.1056G>A) is common (popmax 32.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1056G>A · rs13038893 · VCV261258

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 32.6%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

IVIC 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 -5	GERP -4.7
Overall
CADD	0.758	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 32.6% European (non-Finnish) · 385,165/1,179,936 alleles

Filtering AF 32.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.5%

Overall 29.7% 479,708/1,613,838 alleles · common exomes 435,246/1,461,844 · genomes 44,462/151,994 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	32.7%	3
European (non-Finnish)grpmax	32.6%	3
African / African-American	32.6%	3
Remaining individualsnot grpmax-eligible	28.5%	4
Middle Eastern	25.2%	4
Finnishnot grpmax-eligible	24.6%	4
Ashkenazi Jewishnot grpmax-eligible	22.8%	4
South Asian	17.6%	6
Admixed American	16.8%	6
East Asian	4.16%	24

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala352=
Coding: c.1056G>A
MANE Select: NM_020436
dbSNP: rs13038893
Type: single nucleotide variant
Location: chr20:51791427 (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

IVIC syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Duane-radial ray syndrome

Similar variants

SALL4 p.Ala352Val Uncertain significance ★ ⚠ same residue
SALL4 p.Ala352fs Pathogenic 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

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-ala352 (accessed [today's date]).

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