Is SOX4 p.Ser33Phe (c.98C>T) pathogenic?

SOX4 p.Ser33Phe (c.98C>T) is classified Uncertain significance in SOX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). AlphaMissense: likely pathogenic (0.9198); Absent from gnomAD v4.1.

How common is SOX4 p.Ser33Phe (c.98C>T) in the general population?

SOX4 p.Ser33Phe (c.98C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOX4 p.Ser33Phe (c.98C>T)?

AlphaMissense predicts likely pathogenic (score 0.9198) — an in-silico prediction, not a clinical call.

SOX4 p.Ser33Phe

c.98C>T · VCV3360418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9198 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9198	likely pathogenic
REVEL	0.562	indeterminate
SaProt	LLR -11.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 165 bp · p 0.38 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: SOX4
Protein: p.Ser33Phe
Coding: c.98C>T
MANE Select: NM_003107
Type: single nucleotide variant
Location: chr6:21594632 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 33: the 'disordered' region

Full SOX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SOX4 p.Gln241Ter Likely pathogenic ★★ same type
SOX4 p.Ser347Ter Pathogenic/Likely pathogenic ★★ same type
SOX4 p.Ala145Thr Uncertain significance ★★ ⚠ same type
SOX4 p.Ala231Thr Uncertain significance ★★ ⚠ same type
SOX4 p.Ala234Pro Uncertain significance ★★ ⚠ same type
SOX4 p.Ala253Val Uncertain significance ★★ ⚠ same type
SOX4 p.Arg110Pro Uncertain significance ★★ ⚠ same type
SOX4 p.Gly226Ser Uncertain significance ★★ ⚠ same type

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-ser33phe (accessed [today's date]).

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