Is BCL11B p.Cys61Phe (c.182G>T) pathogenic?

BCL11B p.Cys61Phe (c.182G>T) is classified Uncertain significance in BCL11B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-06). AlphaMissense: likely pathogenic (0.9982); Absent from gnomAD v4.1; Associated with intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities.

How common is BCL11B p.Cys61Phe (c.182G>T) in the general population?

BCL11B p.Cys61Phe (c.182G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCL11B p.Cys61Phe (c.182G>T)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

BCL11B p.Cys61Phe

Q: What condition is associated with BCL11B p.Cys61Phe (c.182G>T)?

BCL11B p.Cys61Phe (c.182G>T) is associated with intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities (ClinVar).

Q: How is Intellectual disability-speech delay-dysmorphic features-T cell abnormalities syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.182G>T · rs2139953989 · VCV1698986

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic · top 6% in BCL11B
REVEL	0.885	moderately pathogenic-leaning
SaProt	LLR -17.89	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 96 kb · p 1.8e-08 · regional, not allelic
Overall
CADD	26.9	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: BCL11B
Protein: p.Cys61Phe
Coding: c.182G>T
MANE Select: NM_138576
dbSNP: rs2139953989
Type: single nucleotide variant
Location: chr14:99257716 (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

Disease context

intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Intellectual disability-speech delay-dysmorphic features-T cell abnormalities syndrome (Orphanet):

Inheritance: Autosomal dominant

Similar variants

BCL11B p.Asn807Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
BCL11B p.Cys808Arg Likely pathogenic ★★ same condition
BCL11B p.Tyr824Ter Likely pathogenic ★★ same condition
BCL11B p.Arg620Cys Uncertain significance ★★ ⚠ same condition
BCL11B p.Glu553Gln Uncertain significance ★★ ⚠ same condition
BCL11B p.Gly515Ser Uncertain significance ★★ ⚠ same condition
BCL11B p.Pro377Leu Uncertain significance ★★ ⚠ same condition
BCL11B p.Pro407Ser 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/bcl11b-p-cys61phe (accessed [today's date]).

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