Is BABAM2 p.Pro348Leu (c.1043C>T) pathogenic?

BABAM2 p.Pro348Leu (c.1043C>T) is classified Uncertain significance in BABAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely pathogenic (0.9805); Very rare (popmax 0.00446%, eas).

How common is BABAM2 p.Pro348Leu (c.1043C>T) in the general population?

BABAM2 p.Pro348Leu (c.1043C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about BABAM2 p.Pro348Leu (c.1043C>T)?

AlphaMissense predicts likely pathogenic (score 0.9805) — an in-silico prediction, not a clinical call.

BABAM2 p.Pro348Leu

c.1043C>T · rs764086199 · VCV2548089

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9805 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9805	likely pathogenic
REVEL	0.494	indeterminate
SaProt	LLR -10.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 444 kb · p 1.7e-05 · regional, not allelic
Overall
CADD	28.2	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 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000274% 4/1,461,862 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,442
European (non-Finnish)	0.000169%	590,002

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.Pro348Leu
Coding: c.1043C>T
MANE Select: NM_199191
dbSNP: rs764086199
Type: single nucleotide variant
Location: chr2:28298446 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.76 · 13 PDB
Residue 348: 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-pro348leu (accessed [today's date]).

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