Is BCR p.Ile413Met (c.1239C>G) pathogenic?

BCR p.Ile413Met (c.1239C>G) is classified Likely benign in BCR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: ambiguous (0.4311); Rare (popmax 0.165%, mid).

How common is BCR p.Ile413Met (c.1239C>G) in the general population?

BCR p.Ile413Met (c.1239C>G) is rare (popmax 0.165%, mid) (gnomAD).

What do computational predictors say about BCR p.Ile413Met (c.1239C>G)?

AlphaMissense predicts ambiguous (score 0.4311) — an in-silico prediction, not a clinical call.

BCR p.Ile413Met

c.1239C>G · rs56321828 · VCV732727

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4311 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.165%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4311	ambiguous
REVEL	0.216	benign-leaning
SaProt	LLR -6.58	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.54	GERP -3.8, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 73 kb · p 1.1e-11 · regional, not allelic
Overall
CADD	22.2	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 0.165% Middle Eastern · 10/6,046 alleles

Filtering AF 0.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0982%

Overall 0.092% 1,465/1,592,832 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.256%	391
Middle Easterngrpmax	0.165%	605
European (non-Finnish)	0.105%	952
Remaining individualsnot grpmax-eligible	0.0937%	1,068
Admixed American	0.0219%	4,563
South Asian	0.0122%	8,205
African / African-American	0.00935%	10,699

Finnish 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: BCR
Protein: p.Ile413Met
Coding: c.1239C>G
MANE Select: NM_004327
dbSNP: rs56321828
Type: single nucleotide variant
Location: chr22:23182199 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.61 · 5 PDB
Residue 413: a UniProt-annotated variant site (in); the 'kinase' region

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

Similar variants

BCR p.Ser356Arg Uncertain significance ★★ ⚠ same type
BCR c.2116-6C>G Benign/Likely benign ★★ same type
BCR c.2116-7C>A Benign/Likely benign ★★ same type
BCR c.2526+7G>T Benign/Likely benign ★★ same type
BCR c.3073-8T>C Benign ★★ same type
BCR c.3183-4G>A Benign ★★ same type
BCR p.Ala1257= Benign/Likely benign ★★ same type
BCR p.Ala152Val Benign ★★ ⚠ 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/bcr-p-ile413met (accessed [today's date]).

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