Is SOX4 p.Ser384Phe (c.1151C>T) pathogenic?

SOX4 p.Ser384Phe (c.1151C>T) is classified Uncertain significance in SOX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: ambiguous (0.3946); Very rare (popmax 0.0027%, afr); Associated with Inborn genetic diseases.

What condition is associated with SOX4 p.Ser384Phe (c.1151C>T)?

SOX4 p.Ser384Phe (c.1151C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SOX4 p.Ser384Phe (c.1151C>T) in the general population?

SOX4 p.Ser384Phe (c.1151C>T) is very rare (popmax 0.0027%, afr) (gnomAD).

What do computational predictors say about SOX4 p.Ser384Phe (c.1151C>T)?

AlphaMissense predicts ambiguous (score 0.3946) — an in-silico prediction, not a clinical call.

SOX4 p.Ser384Phe

c.1151C>T · rs763234364 · VCV3167777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3946 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0027%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3946	ambiguous
REVEL	0.346	indeterminate
SaProt	LLR -10.97	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 2, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,022 bp · p 0.058 · 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

Grpmax group 0.0027% African / African-American · 2/74,208 alleles

Filtering AF 0.000447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000379% 6/1,583,166 alleles · very rare exomes 6/1,430,970 · genomes 0/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0027%	37,104
European (non-Finnish)	0.000343%	291,295

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: SOX4
Protein: p.Ser384Phe
Coding: c.1151C>T
MANE Select: NM_003107
dbSNP: rs763234364
Type: single nucleotide variant
Location: chr6:21595685 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 384: the 'disordered' region

Full SOX4 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

SOX4 p.Ala145Thr Uncertain significance ★★ ⚠ same condition
SOX4 p.Ala253Val Uncertain significance ★★ ⚠ same condition
SOX4 p.Arg110Pro Uncertain significance ★★ ⚠ same condition
SOX4 p.Gly226Ser Uncertain significance ★★ ⚠ same condition
SOX4 p.Leu100Phe Uncertain significance ★★ ⚠ same condition
SOX4 p.Pro214Ser Uncertain significance ★★ ⚠ same condition
SOX4 p.Ser32Ala Uncertain significance ★★ ⚠ same condition
SOX4 p.Arg110= Likely benign ★★ 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/sox4-p-ser384phe (accessed [today's date]).

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