Is BIRC3 p.Cys557Ter (c.1671T>A) pathogenic?

BIRC3 p.Cys557Ter (c.1671T>A) is classified Likely pathogenic in BIRC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-05). Very rare (popmax 8.49e-05%, nfe); Associated with Regional enteritis.

What condition is associated with BIRC3 p.Cys557Ter (c.1671T>A)?

BIRC3 p.Cys557Ter (c.1671T>A) is associated with Regional enteritis (ClinVar).

How common is BIRC3 p.Cys557Ter (c.1671T>A) in the general population?

BIRC3 p.Cys557Ter (c.1671T>A) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

BIRC3 p.Cys557Ter

c.1671T>A · rs774719063 · VCV3906849

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

Regional enteritis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.25	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -0.67	GERP -3.7, phastCons 0.04
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,930 alleles

Overall 6.23e-05% 1/1,604,692 alleles · very rare exomes 1/1,452,406 · genomes 0/152,286 · joint denominator

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: BIRC3
Protein: p.Cys557Ter
Coding: c.1671T>A
MANE Select: NM_001165
dbSNP: rs774719063
Type: single nucleotide variant
Location: chr11:102336958 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 75.13 · 6 PDB

Full BIRC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Regional enteritis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BIRC3 p.Asp530His Likely pathogenic ★ ⚠ same condition
BIRC3 p.Cys588Tyr Likely pathogenic ★ same condition
BIRC3 p.His312Tyr Likely pathogenic ★ same condition
BIRC3 p.Ter605Arg Likely pathogenic ★ same condition
BIRC3 p.Thr35Ala Likely pathogenic ★ same condition
BIRC3 p.Tyr522Ter Likely pathogenic ★ same condition
BIRC3 p.Pro266Arg Uncertain significance ★ same condition
BIRC3 p.Arg401Lys Likely 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/birc3-p-cys557ter (accessed [today's date]).

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