Is BIRC2 p.Asn162Lys (c.486T>G) pathogenic?

BIRC2 p.Asn162Lys (c.486T>G) is classified Uncertain significance in BIRC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). AlphaMissense: likely benign (0.1298); Ultra-rare (popmax 0.0164%, mid).

How common is BIRC2 p.Asn162Lys (c.486T>G) in the general population?

BIRC2 p.Asn162Lys (c.486T>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about BIRC2 p.Asn162Lys (c.486T>G)?

AlphaMissense predicts likely benign (score 0.1298) — an in-silico prediction, not a clinical call.

BIRC2 p.Asn162Lys

c.486T>G · VCV3480683

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1298 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1298	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.18	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 0.88	GERP -3.7, phastCons 0.69
Regional constraint	o/e 1.02	unconstrained · MANE · 1,007 bp · p 0.63 · regional, not allelic
Overall
CADD	19.61	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00155% 25/1,614,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00667%	14,985
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00144%	69,415

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: BIRC2
Protein: p.Asn162Lys
Coding: c.486T>G
MANE Select: NM_001166
Type: single nucleotide variant
Location: chr11:102350340 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.08 · 29 PDB

Full BIRC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BIRC2 p.Ala506Val Benign ★★ same type
BIRC2 p.Ala186Thr Uncertain significance ★ ⚠ same type
BIRC2 p.Ala388Thr Uncertain significance ★ ⚠ same type
BIRC2 p.Ala58Ser Uncertain significance ★ ⚠ same type
BIRC2 p.Arg164Lys Uncertain significance ★ ⚠ same type
BIRC2 p.Arg241Gln Uncertain significance ★ ⚠ same type
BIRC2 p.Arg300Cys Uncertain significance ★ ⚠ same type
BIRC2 p.Arg338Gln 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/birc2-p-asn162lys (accessed [today's date]).

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