Is BCAP29 p.Phe22Leu (c.66C>G) pathogenic?

BCAP29 p.Phe22Leu (c.66C>G) is classified Uncertain significance in BCAP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-21). AlphaMissense: ambiguous (0.5241); Ultra-rare (popmax 0.0166%, mid).

How common is BCAP29 p.Phe22Leu (c.66C>G) in the general population?

BCAP29 p.Phe22Leu (c.66C>G) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about BCAP29 p.Phe22Leu (c.66C>G)?

AlphaMissense predicts ambiguous (score 0.5241) — an in-silico prediction, not a clinical call.

BCAP29 p.Phe22Leu

c.66C>G · rs1303562851 · VCV2233901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5241 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5241	ambiguous
REVEL	0.103	moderately benign-leaning
SaProt	LLR -5.07	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 0.79, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 38 kb · p 0.0063 · regional, not allelic
Overall
CADD	19.36	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 0.0166% Middle Eastern · 1/6,028 alleles

Overall 0.000209% 3/1,437,356 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,028
Remaining individualsnot grpmax-eligible	0.00163%	61,508
European (non-Finnish)	8.55e-05%	1,169,904

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: BCAP29
Protein: p.Phe22Leu
Coding: c.66C>G
MANE Select: NM_018844
dbSNP: rs1303562851
Type: single nucleotide variant
Location: chr7:107580838 (GRCh38)
Gene constraint: LOEUF 1.594 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.51 · 3 PDB

Full BCAP29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/bcap29-p-phe22leu (accessed [today's date]).

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