Is BABAM2 p.Gly50Arg (c.148G>C) pathogenic?

BABAM2 p.Gly50Arg (c.148G>C) is classified Uncertain significance in BABAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-20). AlphaMissense: ambiguous (0.551); Ultra-rare (popmax 0.011%, sas).

How common is BABAM2 p.Gly50Arg (c.148G>C) in the general population?

BABAM2 p.Gly50Arg (c.148G>C) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about BABAM2 p.Gly50Arg (c.148G>C)?

AlphaMissense predicts ambiguous (score 0.551) — an in-silico prediction, not a clinical call.

BABAM2 p.Gly50Arg

c.148G>C · rs531578768 · VCV3132750

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.551 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.551	ambiguous
REVEL	0.262	benign-leaning
SaProt	LLR -9.35	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 444 kb · p 1.7e-05 · regional, not allelic
Overall
CADD	23.5	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 0.011% South Asian · 10/91,058 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.000806% 13/1,613,660 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,106
Remaining individualsnot grpmax-eligible	0.0048%	20,827

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.Gly50Arg
Coding: c.148G>C
MANE Select: NM_199191
dbSNP: rs531578768
Type: single nucleotide variant
Location: chr2:27929851 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.76 · 13 PDB
Residue 50: the 'uev-like 1' 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-gly50arg (accessed [today's date]).

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