Is BIRC2 p.Ala506Val (c.1517C>T) pathogenic?

BIRC2 p.Ala506Val (c.1517C>T) is classified Benign in BIRC2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2020-02-17). AlphaMissense: likely benign (0.2429); Common (popmax 8.09%, mid) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BIRC2 p.Ala506Val (c.1517C>T)?

AlphaMissense predicts likely benign (score 0.2429) — an in-silico prediction, not a clinical call.

BIRC2 p.Ala506Val

Q: How common is BIRC2 p.Ala506Val (c.1517C>T) in the general population?

BIRC2 p.Ala506Val (c.1517C>T) is common (popmax 8.09%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1517C>T · rs34510872 · VCV1261128

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2429 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.09%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2429	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -4.13	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 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 14 kb · p 0.071 · regional, not allelic
Overall
CADD	25.0	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 8.09% Middle Eastern · 489/6,048 alleles

Filtering AF 7.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.26%

Overall 4.79% 77,128/1,610,192 alleles · common exomes 70,163/1,458,110 · genomes 6,965/152,082 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	12.3%	8
Middle Easterngrpmax	8.09%	12
Ashkenazi Jewishnot grpmax-eligible	6.55%	15
European (non-Finnish)	4.98%	20
Remaining individualsnot grpmax-eligible	4.89%	20
Admixed American	4.04%	25
South Asian	1.77%	56
African / African-American	1.57%	64
East Asian	0.00669%	14,945

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: BIRC2
Protein: p.Ala506Val
Coding: c.1517C>T
MANE Select: NM_001166
dbSNP: rs34510872
Type: single nucleotide variant
Location: chr11:102377646 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.08 · 29 PDB
Residue 506: a UniProt-annotated variant site (in); the card domain; an α-helix

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

Similar variants

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
BIRC2 p.Arg338Gly 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-ala506val (accessed [today's date]).

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