Is BSCL2 p.Met121Val (c.361A>G) pathogenic?

BSCL2 p.Met121Val (c.361A>G) is classified Uncertain significance in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-06-29). AlphaMissense: likely benign (0.3206); Very rare (popmax 0.000254%, nfe); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with BSCL2 p.Met121Val (c.361A>G)?

BSCL2 p.Met121Val (c.361A>G) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Met121Val (c.361A>G) in the general population?

BSCL2 p.Met121Val (c.361A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about BSCL2 p.Met121Val (c.361A>G)?

AlphaMissense predicts likely benign (score 0.3206) — an in-silico prediction, not a clinical call.

BSCL2 p.Met121Val

c.361A>G · rs2134740508 · VCV1054215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3206 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
AlphaMissense	0.3206	likely benign
REVEL	0.721	pathogenic-leaning
SaProt	LLR -5.23	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.65 · regional, not allelic
Overall
CADD	23.6	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 M57V vs ClinVar M121V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,912 alleles

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

Overall 0.000205% 3/1,461,660 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: BSCL2
Protein: p.Met121Val
Coding: c.361A>G
MANE Select: NM_001122955
dbSNP: rs2134740508
Type: single nucleotide variant
Location: chr11:62705344 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.09 · 1 PDB

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

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BSCL2 p.Met121Ile Uncertain significance ★ ⚠ same residue
BSCL2 c.1006-2A>C Likely pathogenic ★★ same condition
BSCL2 c.486+1G>A Pathogenic/Likely pathogenic ★★ same condition
BSCL2 p.Ala276Pro Pathogenic ★★ same condition
BSCL2 p.Arg329Ter Pathogenic ★★ same condition
BSCL2 p.Asn152Ser Pathogenic ★★ ⚠ same condition
BSCL2 p.Glu253Ter Pathogenic ★★ same condition
BSCL2 p.Ser154Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition

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-met121val (accessed [today's date]).

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