Is SALL4 p.Pro331Gln (c.992C>A) pathogenic?

SALL4 p.Pro331Gln (c.992C>A) is classified Uncertain significance in SALL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: ambiguous (0.3425); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SALL4 p.Pro331Gln (c.992C>A)?

SALL4 p.Pro331Gln (c.992C>A) is associated with Inborn genetic diseases (ClinVar).

How common is SALL4 p.Pro331Gln (c.992C>A) in the general population?

SALL4 p.Pro331Gln (c.992C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SALL4 p.Pro331Gln (c.992C>A)?

AlphaMissense predicts ambiguous (score 0.3425) — an in-silico prediction, not a clinical call.

SALL4 p.Pro331Gln

c.992C>A · VCV3436916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3425 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3425	ambiguous
REVEL	0.203	benign-leaning
SaProt	LLR -9.08	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.28, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,245 bp · p 1.1e-08 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SALL4
Protein: p.Pro331Gln
Coding: c.992C>A
MANE Select: NM_020436
Type: single nucleotide variant
Location: chr20:51791491 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SALL4 p.Ala118Val Uncertain significance ★★ ⚠ same condition
SALL4 p.Ala254Thr Uncertain significance ★★ ⚠ same condition
SALL4 p.Ala40Val Uncertain significance ★★ ⚠ same condition
SALL4 p.Ala561Thr Uncertain significance ★★ ⚠ same condition
SALL4 p.Arg329Cys Uncertain significance ★★ ⚠ same condition
SALL4 p.Arg586Gly Uncertain significance ★★ ⚠ same condition
SALL4 p.Arg617Gln Uncertain significance ★★ ⚠ same condition
SALL4 p.Arg68Gln 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-pro331gln (accessed [today's date]).

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