Is BIRC6 p.Arg267His (c.800G>A) pathogenic?

BIRC6 p.Arg267His (c.800G>A) is classified Uncertain significance in BIRC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: ambiguous (0.3475); Very rare (popmax 0.00518%, amr).

How common is BIRC6 p.Arg267His (c.800G>A) in the general population?

BIRC6 p.Arg267His (c.800G>A) is very rare (popmax 0.00518%, amr) (gnomAD).

What do computational predictors say about BIRC6 p.Arg267His (c.800G>A)?

AlphaMissense predicts ambiguous (score 0.3475) — an in-silico prediction, not a clinical call.

BIRC6 p.Arg267His

c.800G>A · VCV3260968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3475 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00518%, amr)

Computational evidence

Protein change
AlphaMissense	0.3475	ambiguous
REVEL	0.479	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.17 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 0.00518% Admixed American · 3/57,890 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000681%

Overall 0.000373% 6/1,606,480 alleles · very rare exomes 5/1,454,360 · genomes 1/152,120 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00518%	19,297
African / African-American	0.00402%	24,901

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.Arg267His
Coding: c.800G>A
MANE Select: NM_016252
Type: single nucleotide variant
Location: chr2:32388904 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)

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

Similar variants

BIRC6 p.Gln853Arg Uncertain significance ★★ ⚠ same type
BIRC6 p.Glu4506Asp Uncertain significance ★★ ⚠ same type
BIRC6 c.7409-6T>C Likely benign ★★ same type
BIRC6 p.Ala1549= Benign ★★ same type
BIRC6 p.Ala3622Val Likely benign ★★ same type
BIRC6 p.Ala4466= Benign/Likely benign ★★ same type
BIRC6 p.Arg4605= Benign ★★ same type
BIRC6 p.Asp4607= 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/birc6-p-arg267his (accessed [today's date]).

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