Is BCAM p.Leu409= (c.1227G>T) pathogenic?

BCAM p.Leu409= (c.1227G>T) is classified Benign in BCAM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-27). Common (popmax 5.99%, afr) — too common for a highly-penetrant pathogenic allele.

BCAM p.Leu409=

Q: How common is BCAM p.Leu409= (c.1227G>T) in the general population?

BCAM p.Leu409= (c.1227G>T) is common (popmax 5.99%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1227G>T · rs28399629 · VCV780574

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.99%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -4
Overall
CADD	0.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.99% African / African-American · 4,496/75,014 alleles

Filtering AF 5.85% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.79%

Overall 0.307% 4,958/1,614,074 alleles · common exomes 2,481/1,461,848 · genomes 2,477/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.99%	17
Remaining individualsnot grpmax-eligible	0.342%	292
Admixed American	0.303%	330
Middle Eastern	0.231%	433
South Asian	0.00659%	15,180
European (non-Finnish)	0.00381%	26,222
East Asian	0.00223%	44,870

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: BCAM
Protein: p.Leu409=
Coding: c.1227G>T
MANE Select: NM_005581
dbSNP: rs28399629
Type: single nucleotide variant
Location: chr19:44818773 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.29 · 2 PDB
Residue 409: the ig-like c2-type 2 domain

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

Similar variants

BCAM p.Arg282His Benign ★★ same type
BCAM p.Pro589Leu Likely benign ★★ same type
BCAM p.Thr539Ala Benign ★★ same type
BCAM p.Val381Ile Benign ★★ same type
BCAM p.Val540= Benign ★★ same type
BCAM p.Ala129Ser Uncertain significance ★ ⚠ same type
BCAM p.Ala129Thr Uncertain significance ★ ⚠ same type
BCAM p.Ala132Thr 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/bcam-p-leu409 (accessed [today's date]).

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