Is SOX11 p.Ser71Pro (c.211T>C) pathogenic?

SOX11 p.Ser71Pro (c.211T>C) is classified Likely pathogenic in SOX11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-07). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1; Associated with SOX11-related disorder.

What condition is associated with SOX11 p.Ser71Pro (c.211T>C)?

SOX11 p.Ser71Pro (c.211T>C) is associated with SOX11-related disorder (ClinVar).

How common is SOX11 p.Ser71Pro (c.211T>C) in the general population?

SOX11 p.Ser71Pro (c.211T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOX11 p.Ser71Pro (c.211T>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

SOX11 p.Ser71Pro

c.211T>C · VCV4952566

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SOX11-related disorder

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic ✓ concordant with ClinVar · top 9% in SOX11
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -13.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 262 bp · p 3e-18 · regional, not allelic
Overall
CADD	32.0	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: SOX11
Protein: p.Ser71Pro
Coding: c.211T>C
MANE Select: NM_003108
Type: single nucleotide variant
Location: chr2:5692932 (GRCh38)
Gene constraint: LOEUF 1.148 · pLI 0.09 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.44 · 4 PDB
Residue 71: a DNA-binding region; a UniProt-annotated variant site (in iddmoh)

Full SOX11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SOX11-related disorder

Similar variants

SOX11 p.Pro52Gln Likely pathogenic ★ same condition
SOX11 p.Trp41Ter Likely pathogenic ★ same condition
SOX11 p.Ser354Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
SOX11 p.Lys50Glu Likely pathogenic same condition
SOX11 p.Ser287Cys Uncertain significance ⚠ same condition
SOX11 p.Ser335Cys Uncertain significance ⚠ same condition
SOX11 p.Ser393Pro Uncertain significance ⚠ same condition
SOX11 p.Gly214_Lys215insTer Likely pathogenic ★ 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/sox11-p-ser71pro (accessed [today's date]).

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