Is BCS1L p.Ser271= (c.813C>T) pathogenic?

BCS1L p.Ser271= (c.813C>T) is classified Likely benign in BCS1L (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-08). Ultra-rare (popmax 0.016%, afr).

How common is BCS1L p.Ser271= (c.813C>T) in the general population?

BCS1L p.Ser271= (c.813C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

BCS1L p.Ser271=

c.813C>T · rs146782209 · VCV792788

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.314	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.7	GERP -5
Overall
CADD	4.434	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/75,044 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.00322% 52/1,614,160 alleles · ultra-rare exomes 44/1,461,872 · genomes 8/152,288 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,922
African / African-Americangrpmax	0.016%	6,254
East Asian	0.00668%	14,960
Admixed American	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0064%	15,627
European (non-Finnish)	0.00195%	51,305
South Asian	0.0011%	91,082

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BCS1L
Protein: p.Ser271=
Coding: c.813C>T
MANE Select: NM_001079866
dbSNP: rs146782209
Type: single nucleotide variant
Location: chr2:218662603 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.10

Full BCS1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCS1L c.320+1G>T Pathogenic/Likely pathogenic ★★ same type
BCS1L c.321-2A>G Likely pathogenic ★★ same type
BCS1L c.889+1G>T Pathogenic/Likely pathogenic ★★ same type
BCS1L c.889+2T>G Likely pathogenic ★★ same type
BCS1L c.-50+388C>G Likely pathogenic ★★ same type
BCS1L c.-50+405A>G Pathogenic/Likely pathogenic ★★ same type
BCS1L p.Arg109Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
BCS1L p.Arg114Trp Pathogenic/Likely pathogenic ★★ ⚠ 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/bcs1l-p-ser271 (accessed [today's date]).

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