Is BABAM2 p.Val287Met (c.859G>A) pathogenic?

BABAM2 p.Val287Met (c.859G>A) is classified Uncertain significance in BABAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely pathogenic (0.735); Very rare (popmax 0.00534%, afr).

How common is BABAM2 p.Val287Met (c.859G>A) in the general population?

BABAM2 p.Val287Met (c.859G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about BABAM2 p.Val287Met (c.859G>A)?

AlphaMissense predicts likely pathogenic (score 0.735) — an in-silico prediction, not a clinical call.

BABAM2 p.Val287Met

c.859G>A · rs748807354 · VCV2521636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.735	likely pathogenic
REVEL	0.391	indeterminate
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 444 kb · p 1.7e-05 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 0.00534% African / African-American · 4/74,838 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00192% 31/1,613,420 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,709
South Asian	0.00439%	22,754
European (non-Finnish)	0.00178%	56,181
Admixed American	0.00167%	59,952
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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: BABAM2
Protein: p.Val287Met
Coding: c.859G>A
MANE Select: NM_199191
dbSNP: rs748807354
Type: single nucleotide variant
Location: chr2:28244787 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.76 · 13 PDB
Residue 287: the 'uev-like 2' region; a β-strand

Full BABAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BABAM2 p.Val287Leu Uncertain significance ★ ⚠ same residue
BABAM2 c.1089-11028A>G Uncertain significance ★ same type
BABAM2 c.1089-11081G>A Uncertain significance ★ same type
BABAM2 c.1089-11108C>G Uncertain significance ★ same type
BABAM2 c.1089-11127G>A Uncertain significance ★ same type
BABAM2 c.1089-11144C>T Uncertain significance ★ same type
BABAM2 c.1089-11169C>G Uncertain significance ★ same type
BABAM2 p.Arg131Cys 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/babam2-p-val287met (accessed [today's date]).

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