Is BCLAF1 p.Ser36Pro (c.106T>C) pathogenic?

BCLAF1 p.Ser36Pro (c.106T>C) is classified Uncertain significance in BCLAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-07). AlphaMissense: likely pathogenic (0.8724); Absent from gnomAD v4.1.

How common is BCLAF1 p.Ser36Pro (c.106T>C) in the general population?

BCLAF1 p.Ser36Pro (c.106T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCLAF1 p.Ser36Pro (c.106T>C)?

AlphaMissense predicts likely pathogenic (score 0.8724) — an in-silico prediction, not a clinical call.

BCLAF1 p.Ser36Pro

c.106T>C · rs765304506 · VCV2559143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8724 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8724	likely pathogenic
REVEL	0.284	benign-leaning
SaProt	LLR -10.20	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 1,293 bp · p 7.7e-06 · regional, not allelic
Overall
CADD	29.2	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

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: BCLAF1
Protein: p.Ser36Pro
Coding: c.106T>C
MANE Select: NM_014739
dbSNP: rs765304506
Type: single nucleotide variant
Location: chr6:136278775 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 47.04 · 2 PDB
Residue 36: the 'disordered' region

Full BCLAF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCLAF1 p.Gly210Ser Benign/Likely benign ★★ same type
BCLAF1 c.2397+1G>C Uncertain significance ★ same type
BCLAF1 p.Ala169Thr Uncertain significance ★ ⚠ same type
BCLAF1 p.Ala310Val Uncertain significance ★ ⚠ same type
BCLAF1 p.Ala669Val Uncertain significance ★ ⚠ same type
BCLAF1 p.Arg107Gln Uncertain significance ★ ⚠ same type
BCLAF1 p.Arg111His Uncertain significance ★ ⚠ same type
BCLAF1 p.Arg126Lys 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/bclaf1-p-ser36pro (accessed [today's date]).

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