Is BCL11B p.Pro320Ser (c.958C>T) pathogenic?

BCL11B p.Pro320Ser (c.958C>T) is classified Uncertain significance in BCL11B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-08). AlphaMissense: likely pathogenic (0.6095); Very rare (popmax 0.0026%, eas).

How common is BCL11B p.Pro320Ser (c.958C>T) in the general population?

BCL11B p.Pro320Ser (c.958C>T) is very rare (popmax 0.0026%, eas) (gnomAD).

What do computational predictors say about BCL11B p.Pro320Ser (c.958C>T)?

AlphaMissense predicts likely pathogenic (score 0.6095) — an in-silico prediction, not a clinical call.

BCL11B p.Pro320Ser

c.958C>T · VCV3368468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6095 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0026%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6095	likely pathogenic
REVEL	0.251	benign-leaning
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 96 kb · p 1.8e-08 · regional, not allelic
Overall
CADD	27.8	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 0.0026% East Asian · 1/38,468 alleles

Overall 0.000136% 2/1,469,142 alleles · very rare exomes 2/1,316,968 · genomes 0/152,174 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0026%	38,468
European (non-Finnish)	8.97e-05%	1,114,784

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: BCL11B
Protein: p.Pro320Ser
Coding: c.958C>T
MANE Select: NM_138576
Type: single nucleotide variant
Location: chr14:99175878 (GRCh38)
Gene constraint: LOEUF 0.462 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.76 · 6 PDB

Full BCL11B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCL11B p.Asn807Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
BCL11B p.Cys808Arg Likely pathogenic ★★ same type
BCL11B p.Tyr824Ter Likely pathogenic ★★ same type
BCL11B p.Ala152Val Uncertain significance ★★ ⚠ same type
BCL11B p.Ala188Thr Uncertain significance ★★ ⚠ same type
BCL11B p.Ala339Val Uncertain significance ★★ ⚠ same type
BCL11B p.Ala424Asp Uncertain significance ★★ ⚠ same type
BCL11B p.Ala579Thr 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/bcl11b-p-pro320ser (accessed [today's date]).

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