Is BSCL2 p.Ser207Cys (c.620C>G) pathogenic?

BSCL2 p.Ser207Cys (c.620C>G) is classified Uncertain significance in BSCL2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-26). AlphaMissense: likely benign (0.2533); Very rare (popmax 0.00441%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BSCL2 p.Ser207Cys (c.620C>G)?

BSCL2 p.Ser207Cys (c.620C>G) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Ser207Cys (c.620C>G) in the general population?

BSCL2 p.Ser207Cys (c.620C>G) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about BSCL2 p.Ser207Cys (c.620C>G)?

AlphaMissense predicts likely benign (score 0.2533) — an in-silico prediction, not a clinical call.

BSCL2 p.Ser207Cys

c.620C>G · rs746973203 · VCV1487540

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2533 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2533	likely benign
REVEL	0.614	indeterminate
SaProt	LLR -14.44	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.8	GERP 1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 2,247 bp · p 9.1e-06 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S143C vs ClinVar S207C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00441% European (non-Finnish) · 52/1,180,024 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00341% 55/1,613,934 alleles · very rare exomes 50/1,461,882 · genomes 5/152,052 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,693
Admixed American	0.00167%	59,972
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00134%	74,880

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: BSCL2
Protein: p.Ser207Cys
Coding: c.620C>G
MANE Select: NM_001122955
dbSNP: rs746973203
Type: single nucleotide variant
Location: chr11:62694578 (GRCh38)

Full BSCL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 2

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/bscl2-p-ser207cys (accessed [today's date]).

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