Is BHMT2 p.Pro3Leu (c.8C>T) pathogenic?

BHMT2 p.Pro3Leu (c.8C>T) is classified Uncertain significance in BHMT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely benign (0.1071); Absent from gnomAD v4.1.

How common is BHMT2 p.Pro3Leu (c.8C>T) in the general population?

BHMT2 p.Pro3Leu (c.8C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BHMT2 p.Pro3Leu (c.8C>T)?

AlphaMissense predicts likely benign (score 0.1071) — an in-silico prediction, not a clinical call.

BHMT2 p.Pro3Leu

c.8C>T · VCV4207629

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1071 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,435,708)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1071	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.23	GERP -0.78
Regional constraint	o/e 0.90	unconstrained · MANE · 19 kb · p 0.033 · regional, not allelic
Overall
CADD	18.97	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,435,708). 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: BHMT2
Protein: p.Pro3Leu
Coding: c.8C>T
MANE Select: NM_017614
Type: single nucleotide variant
Location: chr5:79069790 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.82

Full BHMT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BHMT2 p.Ala66Val Benign ★★ ⚠ same type
BHMT2 p.Ala126Gly Uncertain significance ★ ⚠ same type
BHMT2 p.Ala233Val Uncertain significance ★ ⚠ same type
BHMT2 p.Ala244Val Uncertain significance ★ ⚠ same type
BHMT2 p.Ala279Thr Uncertain significance ★ ⚠ same type
BHMT2 p.Ala98Thr Uncertain significance ★ ⚠ same type
BHMT2 p.Arg16Cys Uncertain significance ★ ⚠ same type
BHMT2 p.Arg16His Uncertain significance ★ ⚠ same type

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/bhmt2-p-pro3leu (accessed [today's date]).

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