Is BCAM p.Pro589Leu (c.1766C>T) pathogenic?

BCAM p.Pro589Leu (c.1766C>T) is classified Likely benign in BCAM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-23). AlphaMissense: likely benign (0.0744); Rare (popmax 0.573%, nfe).

How common is BCAM p.Pro589Leu (c.1766C>T) in the general population?

BCAM p.Pro589Leu (c.1766C>T) is rare (popmax 0.573%, nfe) (gnomAD).

What do computational predictors say about BCAM p.Pro589Leu (c.1766C>T)?

AlphaMissense predicts likely benign (score 0.0744) — an in-silico prediction, not a clinical call.

BCAM p.Pro589Leu

c.1766C>T · rs199854072 · VCV2650087

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0744 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.573%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0744	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.51 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.5	GERP 0.64, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	20.4	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 0.573% European (non-Finnish) · 6,154/1,073,308 alleles

Filtering AF 0.561% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.556%

Overall 0.513% 7,198/1,403,838 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.842%	119
European (non-Finnish)grpmax	0.573%	174
Middle Eastern	0.545%	183
Remaining individualsnot grpmax-eligible	0.517%	193
Finnishnot grpmax-eligible	0.482%	208
South Asian	0.314%	319
Admixed American	0.228%	439
African / African-American	0.0733%	1,365

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro589Leu
Coding: c.1766C>T
MANE Select: NM_005581
dbSNP: rs199854072
Type: single nucleotide variant
Location: chr19:44820707 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.29 · 2 PDB
Residue 589: the 'disordered' region

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

Similar variants

BCAM p.Arg282His Benign ★★ ⚠ same type
BCAM p.Leu409= 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-pro589leu (accessed [today's date]).

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