Is CBS p.Ala237Val (c.710C>T) pathogenic?

CBS p.Ala237Val (c.710C>T) is classified Uncertain significance in CBS (ClinVar, Single submitter, 2 submitters; last evaluated 2018-05-24). AlphaMissense: likely pathogenic (0.6903); Very rare (popmax 0.00149%, afr); Associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED.

What condition is associated with CBS p.Ala237Val (c.710C>T)?

CBS p.Ala237Val (c.710C>T) is associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, classic homocystinuria (ClinVar).

How common is CBS p.Ala237Val (c.710C>T) in the general population?

CBS p.Ala237Val (c.710C>T) is very rare (popmax 0.00149%, afr) (gnomAD).

What do computational predictors say about CBS p.Ala237Val (c.710C>T)?

AlphaMissense predicts likely pathogenic (score 0.6903) — an in-silico prediction, not a clinical call.

CBS p.Ala237Val

c.710C>T · rs1568931765 · VCV568240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00149%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Computational evidence

Protein change
AlphaMissense	0.6903	likely pathogenic
REVEL	0.956	strongly pathogenic-leaning
SaProt	LLR -11.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 11 kb · p 6.7e-07 · regional, not allelic
Overall
CADD	26.1	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 0.00149% African / African-American · 1/67,220 alleles

Overall 7.04e-05% 1/1,419,630 alleles · very rare exomes 1/1,291,808 · genomes 0/127,822 · 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: CBS
Protein: p.Ala237Val
Coding: c.710C>T
MANE Select: NM_000071
dbSNP: rs1568931765
Type: single nucleotide variant
Location: chr21:43065229 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 237: an α-helix

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

Also linked: classic homocystinuria

Similar variants

CBS p.Ala237Thr Uncertain significance ★ ⚠ 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
CBS c.1552+1G>A 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/cbs-p-ala237val (accessed [today's date]).

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