Is BIRC6 p.Ser3427Phe (c.10280C>T) pathogenic?

BIRC6 p.Ser3427Phe (c.10280C>T) is classified Uncertain significance in BIRC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-11). AlphaMissense: likely pathogenic (0.9946); Absent from gnomAD v4.1; Associated with BIRC6-related disorder.

What condition is associated with BIRC6 p.Ser3427Phe (c.10280C>T)?

BIRC6 p.Ser3427Phe (c.10280C>T) is associated with BIRC6-related disorder (ClinVar).

How common is BIRC6 p.Ser3427Phe (c.10280C>T) in the general population?

BIRC6 p.Ser3427Phe (c.10280C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BIRC6 p.Ser3427Phe (c.10280C>T)?

AlphaMissense predicts likely pathogenic (score 0.9946) — an in-silico prediction, not a clinical call.

BIRC6 p.Ser3427Phe

c.10280C>T · rs2473622442 · VCV2631827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9946 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

BIRC6-related disorder

Computational evidence

Protein change
AlphaMissense	0.9946	likely pathogenic · top 9% in BIRC6
REVEL	0.611	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.20	acceptor loss, 42 bp away · masked 0 · deltas
Pangolin	Δ0.28	loss · gain 0.21 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 34 kb · p 0.095 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BIRC6
Protein: p.Ser3427Phe
Coding: c.10280C>T
MANE Select: NM_016252
dbSNP: rs2473622442
Type: single nucleotide variant
Location: chr2:32510568 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)

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.Asp3819Tyr Uncertain significance same condition
BIRC6 p.His3051Leu 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-ser3427phe (accessed [today's date]).

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