Is BIRC3 p.Glu438Asp (c.1314A>C) pathogenic?

BIRC3 p.Glu438Asp (c.1314A>C) is classified Uncertain significance in BIRC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.1122); Very rare (popmax 0.00171%, amr).

How common is BIRC3 p.Glu438Asp (c.1314A>C) in the general population?

BIRC3 p.Glu438Asp (c.1314A>C) is very rare (popmax 0.00171%, amr) (gnomAD).

What do computational predictors say about BIRC3 p.Glu438Asp (c.1314A>C)?

AlphaMissense predicts likely benign (score 0.1122) — an in-silico prediction, not a clinical call.

BIRC3 p.Glu438Asp

c.1314A>C · rs767698113 · VCV2257411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1122	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -7.96	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 2.1	GERP -0.5, phastCons 0.79
Regional constraint	o/e 1.05	unconstrained · MANE · 8,854 bp · p 0.44 · regional, not allelic
Overall
CADD	15.68	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 0.00171% Admixed American · 1/58,646 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000808% 13/1,608,460 alleles · very rare exomes 13/1,456,120 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00171%	58,646
European (non-Finnish)	0.00102%	98,190

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.Glu438Asp
Coding: c.1314A>C
MANE Select: NM_001165
dbSNP: rs767698113
Type: single nucleotide variant
Location: chr11:102331231 (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

Similar variants

BIRC3 p.Arg401Lys Likely benign ★★ same type
BIRC3 p.Arg555= Benign ★★ same type
BIRC3 p.Lys87= Benign ★★ same type
BIRC3 p.Asp530His Likely pathogenic ★ ⚠ same type
BIRC3 p.Cys557Ter Likely pathogenic ★ same type
BIRC3 p.Cys588Tyr Likely pathogenic ★ same type
BIRC3 p.His312Tyr Likely pathogenic ★ same type
BIRC3 p.Ter605Arg Likely pathogenic ★ 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-glu438asp (accessed [today's date]).

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