Is BAIAP2L2 p.Pro472Arg (c.1415C>G) pathogenic?

BAIAP2L2 p.Pro472Arg (c.1415C>G) is classified Uncertain significance in BAIAP2L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.1224); Very rare (popmax 0.00334%, amr).

How common is BAIAP2L2 p.Pro472Arg (c.1415C>G) in the general population?

BAIAP2L2 p.Pro472Arg (c.1415C>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about BAIAP2L2 p.Pro472Arg (c.1415C>G)?

AlphaMissense predicts likely benign (score 0.1224) — an in-silico prediction, not a clinical call.

BAIAP2L2 p.Pro472Arg

c.1415C>G · rs557966274 · VCV3132879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1224 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1224	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -8.43	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 7.1	GERP 1.2, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 25 kb · p 0.0005 · regional, not allelic
Overall
CADD	21.9	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 0.00334% Admixed American · 2/59,850 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000206% 3/1,458,712 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,925
Finnishnot grpmax-eligible	0.00158%	63,282

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: BAIAP2L2
Protein: p.Pro472Arg
Coding: c.1415C>G
MANE Select: NM_025045
dbSNP: rs557966274
Type: single nucleotide variant
Location: chr22:38086294 (GRCh38)
Gene constraint: LOEUF 1.468 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.34
Residue 472: the 'disordered' region

Full BAIAP2L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAIAP2L2 p.Ala163Val Uncertain significance ★ ⚠ same type
BAIAP2L2 p.Ala222Thr Uncertain significance ★ ⚠ same type
BAIAP2L2 p.Ala26Thr Uncertain significance ★ ⚠ same type
BAIAP2L2 p.Ala326Thr Uncertain significance ★ ⚠ same type
BAIAP2L2 p.Ala331Thr Uncertain significance ★ ⚠ same type
BAIAP2L2 p.Ala380Val Uncertain significance ★ ⚠ same type
BAIAP2L2 p.Ala47Val Uncertain significance ★ ⚠ same type
BAIAP2L2 p.Ala62Thr 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/baiap2l2-p-pro472arg (accessed [today's date]).

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