Is BCLAF1 p.Ser243Cys (c.728C>G) pathogenic?

BCLAF1 p.Ser243Cys (c.728C>G) is classified Uncertain significance in BCLAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.1554); Ultra-rare (popmax 0.0166%, sas).

How common is BCLAF1 p.Ser243Cys (c.728C>G) in the general population?

BCLAF1 p.Ser243Cys (c.728C>G) is ultra-rare (popmax 0.0166%, sas) (gnomAD).

What do computational predictors say about BCLAF1 p.Ser243Cys (c.728C>G)?

AlphaMissense predicts likely benign (score 0.1554) — an in-silico prediction, not a clinical call.

BCLAF1 p.Ser243Cys

c.728C>G · VCV4202934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1554 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1554	likely benign
REVEL	0.335	indeterminate
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 223 bp · p 0.0066 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0166% South Asian · 15/90,216 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00828%

Overall 0.000933% 15/1,608,190 alleles · ultra-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.Ser243Cys
Coding: c.728C>G
MANE Select: NM_014739
Type: single nucleotide variant
Location: chr6:136278153 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 47.04 · 2 PDB
Residue 243: 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-ser243cys (accessed [today's date]).

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