Is BABAM1 p.Arg212Pro (c.635G>C) pathogenic?

BABAM1 p.Arg212Pro (c.635G>C) is classified Uncertain significance in BABAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely pathogenic (0.9993); Very rare (popmax 0.00034%, nfe).

How common is BABAM1 p.Arg212Pro (c.635G>C) in the general population?

BABAM1 p.Arg212Pro (c.635G>C) is very rare (popmax 0.00034%, nfe) (gnomAD).

What do computational predictors say about BABAM1 p.Arg212Pro (c.635G>C)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

BABAM1 p.Arg212Pro

c.635G>C · rs201681717 · VCV2517231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic · top 1% in BABAM1
REVEL	0.676	pathogenic-leaning
SaProt	LLR -15.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 0.99, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 10 kb · p 0.049 · regional, not allelic
Overall
CADD	33.0	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 0.00034% European (non-Finnish) · 4/1,176,104 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000275% 4/1,452,886 alleles · very rare

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: BABAM1
Protein: p.Arg212Pro
Coding: c.635G>C
MANE Select: NM_014173
dbSNP: rs201681717
Type: single nucleotide variant
Location: chr19:17276560 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 79.21 · 10 PDB
Residue 212: the 'vwfa-like' region; a β-strand

Full BABAM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BABAM1 p.Arg212His Uncertain significance ★ ⚠ same residue
BABAM1 c.-13-45C>T Benign ★★ same type
BABAM1 p.Ala283Thr Uncertain significance ★ ⚠ same type
BABAM1 p.Arg219Cys Uncertain significance ★ ⚠ same type
BABAM1 p.Arg26Cys Uncertain significance ★ ⚠ same type
BABAM1 p.Arg85Gln Uncertain significance ★ ⚠ same type
BABAM1 p.Asn122Ser Uncertain significance ★ ⚠ same type
BABAM1 p.Asn201Lys 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/babam1-p-arg212pro (accessed [today's date]).

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