Is CBS p.Arg379Gln (c.1136G>A) pathogenic?

CBS p.Arg379Gln (c.1136G>A) is classified Pathogenic in CBS (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-17). AlphaMissense: ambiguous (0.4834); Absent from gnomAD v4.1; Associated with homocystinuria.

What condition is associated with CBS p.Arg379Gln (c.1136G>A)?

CBS p.Arg379Gln (c.1136G>A) is associated with homocystinuria, classic homocystinuria (ClinVar).

How common is CBS p.Arg379Gln (c.1136G>A) in the general population?

CBS p.Arg379Gln (c.1136G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBS p.Arg379Gln (c.1136G>A)?

AlphaMissense predicts ambiguous (score 0.4834) — an in-silico prediction, not a clinical call.

CBS p.Arg379Gln

c.1136G>A · rs763036586 · VCV188825

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.4834 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 24,644)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

homocystinuria

Computational evidence

Protein change
AlphaMissense	0.4834	ambiguous
REVEL	0.821	moderately pathogenic-leaning
SaProt	LLR -14.51	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 11 kb · p 6.7e-07 · regional, not allelic
Overall
CADD	25.5	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

No allele count reported in gnomAD v4.1 (AN 24,644). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CBS
Protein: p.Arg379Gln
Coding: c.1136G>A
MANE Select: NM_000071
dbSNP: rs763036586
Type: single nucleotide variant
Location: chr21:43060450 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 379: a UniProt-annotated variant site (in cbsd; exhibits an activity lower than 4% of the wild-type enzyme; absent capacity to form multimeric quaternary structure); a UniProt-annotated variant site (in cbsd); an α-helix

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

Disease context

homocystinuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: classic homocystinuria

Similar variants

CBS p.Arg379Trp Pathogenic/Likely pathogenic ★★ same residue
CBS p.Arg379Gly Likely pathogenic ★ same residue
CBS c.1145+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS c.1223+1G>T Pathogenic ★★ same condition
CBS c.1224-2A>C Pathogenic ★★ same condition
CBS c.1358+1G>A Pathogenic ★★ same condition
CBS c.1359-1G>C Pathogenic/Likely pathogenic ★★ same condition
CBS c.1468-1G>A 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-arg379gln (accessed [today's date]).

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