Is BCAM p.Pro39Leu (c.116C>T) pathogenic?

BCAM p.Pro39Leu (c.116C>T) is classified Likely benign in BCAM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-10). AlphaMissense: likely benign (0.1289); Rare (popmax 0.348%, eas); Associated with BCAM-related disorder.

What condition is associated with BCAM p.Pro39Leu (c.116C>T)?

BCAM p.Pro39Leu (c.116C>T) is associated with BCAM-related disorder (ClinVar).

How common is BCAM p.Pro39Leu (c.116C>T) in the general population?

BCAM p.Pro39Leu (c.116C>T) is rare (popmax 0.348%, eas) (gnomAD).

What do computational predictors say about BCAM p.Pro39Leu (c.116C>T)?

AlphaMissense predicts likely benign (score 0.1289) — an in-silico prediction, not a clinical call.

BCAM p.Pro39Leu

c.116C>T · rs141053619 · VCV3040212

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1289 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.348%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BCAM-related disorder

Computational evidence

Protein change
AlphaMissense	0.1289	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -9.48	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 2.6	GERP 2, phastCons 0.022
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	24.2	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 0.348% East Asian · 156/44,868 alleles

Filtering AF 0.303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.286%

Overall 0.0108% 174/1,612,844 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.348%	288
Remaining individualsnot grpmax-eligible	0.00962%	10,398
African / African-American	0.004%	24,991
South Asian	0.0033%	30,343
Admixed American	0.00167%	59,992
European (non-Finnish)	0.000424%	235,985

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.Pro39Leu
Coding: c.116C>T
MANE Select: NM_005581
dbSNP: rs141053619
Type: single nucleotide variant
Location: chr19:44811258 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.29 · 2 PDB
Residue 39: a β-strand; the ig-like v-type 1 domain

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

Disease context

BCAM-related disorder

Similar variants

BCAM c.1764-4C>T Likely benign same condition
BCAM c.1882-9G>A Likely benign same condition
BCAM c.433+8T>A Likely benign same condition
BCAM p.Ala238= Benign same condition
BCAM p.Cys237= Benign same condition
BCAM p.Lys451Gln Likely benign same condition
BCAM p.Met204Lys Likely benign ⚠ same condition
BCAM p.Ser332= Likely benign same condition

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-pro39leu (accessed [today's date]).

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