Is BCS1L p.Ser262Pro (c.784T>C) pathogenic?

BCS1L p.Ser262Pro (c.784T>C) is classified Uncertain significance in BCS1L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely pathogenic (0.9539); Very rare (popmax 0.000254%, nfe).

How common is BCS1L p.Ser262Pro (c.784T>C) in the general population?

BCS1L p.Ser262Pro (c.784T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about BCS1L p.Ser262Pro (c.784T>C)?

AlphaMissense predicts likely pathogenic (score 0.9539) — an in-silico prediction, not a clinical call.

BCS1L p.Ser262Pro

c.784T>C · VCV4959816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9539 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9539	likely pathogenic
REVEL	0.922	moderately pathogenic-leaning
SaProt	LLR -14.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 2,395 bp · p 3.2e-10 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000254% European (non-Finnish) · 3/1,180,052 alleles

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

Overall 0.000186% 3/1,614,208 alleles · very rare exomes 3/1,461,882 · genomes 0/152,326 · joint denominator

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.Ser262Pro
Coding: c.784T>C
MANE Select: NM_001079866
Type: single nucleotide variant
Location: chr2:218662574 (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-ser262pro (accessed [today's date]).

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