Is CBS p.Gly307Val (c.920G>T) pathogenic?

CBS p.Gly307Val (c.920G>T) is classified Likely pathogenic in CBS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-29). AlphaMissense: likely pathogenic (0.9816); Absent from gnomAD v4.1; Associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED.

What condition is associated with CBS p.Gly307Val (c.920G>T)?

CBS p.Gly307Val (c.920G>T) is associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED (ClinVar).

How common is CBS p.Gly307Val (c.920G>T) in the general population?

CBS p.Gly307Val (c.920G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBS p.Gly307Val (c.920G>T)?

AlphaMissense predicts likely pathogenic (score 0.9816) — an in-silico prediction, not a clinical call.

CBS p.Gly307Val

c.920G>T · rs2517428448 · VCV2740024

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9816 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Computational evidence

Protein change
AlphaMissense	0.9816	likely pathogenic ✓ concordant with ClinVar · top 4% in CBS
REVEL	0.98	strongly pathogenic-leaning
SaProt	LLR -16.50	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 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 11 kb · p 6.7e-07 · regional, not allelic
Overall
CADD	27.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CBS
Protein: p.Gly307Val
Coding: c.920G>T
MANE Select: NM_000071
dbSNP: rs2517428448
Type: single nucleotide variant
Location: chr21:43062987 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 307: a UniProt-annotated variant site (in cbsd; moderate to severe form; linked with d-534; common mutation; loss of cystathionine beta-synthase activity; impaired stimulation by adomet and adohcy; no effect on homotetramer formation)

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

Disease context

HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CBS p.Gly307Ala Likely pathogenic ★ same residue
CBS p.Gly307Asp Likely pathogenic ★ same residue
CBS p.Gly307= Likely benign ★ same residue
CBS p.Gly307Ser Pathogenic ★★ same residue
CBS c.1145+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS c.1223+1G>T Pathogenic ★★ same condition
CBS c.1552+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS c.451+1G>T 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/cbs-p-gly307val (accessed [today's date]).

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