Is BCLAF1 p.Glu641= (c.1923A>G) pathogenic?

BCLAF1 p.Glu641= (c.1923A>G) is classified Likely benign in BCLAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-20). Very rare (popmax 0.000255%, nfe).

How common is BCLAF1 p.Glu641= (c.1923A>G) in the general population?

BCLAF1 p.Glu641= (c.1923A>G) is very rare (popmax 0.000255%, nfe) (gnomAD).

BCLAF1 p.Glu641=

c.1923A>G · rs1467913885 · VCV750536

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.49	GERP -4.2, phastCons 0.1
Overall
CADD	2.306	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,178,626 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,460,108 alleles · very rare

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: BCLAF1
Protein: p.Glu641=
Coding: c.1923A>G
MANE Select: NM_014739
dbSNP: rs1467913885
Type: single nucleotide variant
Location: chr6:136273117 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 47.04 · 2 PDB
Residue 641: 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-glu641 (accessed [today's date]).

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