Is BABAM2 p.Val330Ile (c.988G>A) pathogenic?

BABAM2 p.Val330Ile (c.988G>A) is classified Uncertain significance in BABAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.0847); Very rare (popmax 0.00439%, sas).

How common is BABAM2 p.Val330Ile (c.988G>A) in the general population?

BABAM2 p.Val330Ile (c.988G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about BABAM2 p.Val330Ile (c.988G>A)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

BABAM2 p.Val330Ile

c.988G>A · rs776406129 · VCV3132758

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -8.72	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 4.5	GERP 0.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 444 kb · p 1.7e-05 · regional, not allelic
Overall
CADD	18.11	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

Grpmax group 0.00439% South Asian · 4/91,068 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00273% 44/1,613,852 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,767
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00305%	32,777
African / African-American	0.00267%	37,439

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.Val330Ile
Coding: c.988G>A
MANE Select: NM_199191
dbSNP: rs776406129
Type: single nucleotide variant
Location: chr2:28298391 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.76 · 13 PDB
Residue 330: the 'uev-like 2' region

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

Similar variants

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
BABAM2 p.Arg133Gln 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-val330ile (accessed [today's date]).

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