Is BCLAF1 p.Arg271Ser (c.813G>T) pathogenic?

BCLAF1 p.Arg271Ser (c.813G>T) is classified Pathogenic in BCLAF1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.6189); Very rare (popmax 0.000426%, nfe); Associated with Pulmonary artery atresia.

What condition is associated with BCLAF1 p.Arg271Ser (c.813G>T)?

BCLAF1 p.Arg271Ser (c.813G>T) is associated with Pulmonary artery atresia (ClinVar).

How common is BCLAF1 p.Arg271Ser (c.813G>T) in the general population?

BCLAF1 p.Arg271Ser (c.813G>T) is very rare (popmax 0.000426%, nfe) (gnomAD).

What do computational predictors say about BCLAF1 p.Arg271Ser (c.813G>T)?

AlphaMissense predicts likely pathogenic (score 0.6189) — an in-silico prediction, not a clinical call.

BCLAF1 p.Arg271Ser

c.813G>T · rs779302959 · VCV1696857

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6189 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000426%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Pulmonary artery atresia

Computational evidence

Protein change
AlphaMissense	0.6189	likely pathogenic ✓ concordant with ClinVar
REVEL	0.249	benign-leaning
SaProt	LLR -6.88	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 -0.12	GERP -4.3, phastCons 0.57
Regional constraint	o/e 0.14	constrained · MANE · 86 bp · p 3.9e-07 · regional, not allelic
Overall
CADD	20.5	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 0.000426% European (non-Finnish) · 5/1,173,448 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000344% 5/1,452,172 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.Arg271Ser
Coding: c.813G>T
MANE Select: NM_014739
dbSNP: rs779302959
Type: single nucleotide variant
Location: chr6:136278068 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 47.04 · 2 PDB
Residue 271: the 'disordered' region

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

Disease context

Pulmonary artery atresia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCLAF1 p.Gln165Lys Pathogenic ⚠ same condition
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

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-arg271ser (accessed [today's date]).

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