Is BIRC6 p.Ser4265= (c.12795C>T) pathogenic?

BIRC6 p.Ser4265= (c.12795C>T) is classified Likely benign in BIRC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-24). Ultra-rare (popmax 0.0495%, mid); Associated with BIRC6-related disorder.

What condition is associated with BIRC6 p.Ser4265= (c.12795C>T)?

BIRC6 p.Ser4265= (c.12795C>T) is associated with BIRC6-related disorder (ClinVar).

How common is BIRC6 p.Ser4265= (c.12795C>T) in the general population?

BIRC6 p.Ser4265= (c.12795C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

BIRC6 p.Ser4265=

c.12795C>T · rs775276590 · VCV3038499

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Conditions

BIRC6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.013	GERP -3.8, phastCons 0.26
Overall
CADD	2.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,060 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00899%

Overall 0.00645% 104/1,612,860 alleles · ultra-rare exomes 98/1,460,754 · genomes 6/152,106 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,020
South Asian	0.0176%	5,690
Remaining individualsnot grpmax-eligible	0.0112%	8,921
European (non-Finnish)	0.00611%	16,376
East Asian	0.00446%	22,428
African / African-American	0.004%	24,985
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596

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: BIRC6
Protein: p.Ser4265=
Coding: c.12795C>T
MANE Select: NM_016252
dbSNP: rs775276590
Type: single nucleotide variant
Location: chr2:32545845 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Residue 4265: the 'disordered' region

Full BIRC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BIRC6-related disorder

Similar variants

BIRC6 p.Gln853Arg Uncertain significance ★★ ⚠ same condition
BIRC6 p.Glu4506Asp Uncertain significance ★★ ⚠ same condition
BIRC6 p.Arg1075Gln Uncertain significance ★ ⚠ same condition
BIRC6 p.Asp386Glu Uncertain significance ★ same condition
BIRC6 p.Asp673His Uncertain significance ★ same condition
BIRC6 p.Ser1258Ala Uncertain significance ★ ⚠ same condition
BIRC6 p.Ser3427Phe Uncertain significance ★ same condition
BIRC6 p.Asp3819Tyr Uncertain significance same condition

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/birc6-p-ser4265 (accessed [today's date]).

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