Is BIRC6 p.Val1732Ile (c.5194G>A) pathogenic?

BIRC6 p.Val1732Ile (c.5194G>A) is classified Benign in BIRC6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0668); Low-frequency (popmax 1.09%, nfe).

How common is BIRC6 p.Val1732Ile (c.5194G>A) in the general population?

BIRC6 p.Val1732Ile (c.5194G>A) is low-frequency (popmax 1.09%, nfe) (gnomAD).

What do computational predictors say about BIRC6 p.Val1732Ile (c.5194G>A)?

AlphaMissense predicts likely benign (score 0.0668) — an in-silico prediction, not a clinical call.

BIRC6 p.Val1732Ile

c.5194G>A · rs61757640 · VCV788639

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0668 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.09%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0668	likely benign
REVEL	0.209	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 69 kb · p 0.5 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.09% European (non-Finnish) · 12,808/1,179,862 alleles

Filtering AF 1.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.06%

Overall 0.94% 15,179/1,613,964 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.42%	41
European (non-Finnish)grpmax	1.09%	92
Remaining individualsnot grpmax-eligible	0.776%	129
Admixed American	0.278%	359
African / African-American	0.172%	582
Middle Eastern	0.132%	758
Ashkenazi Jewishnot grpmax-eligible	0.0777%	1,287
South Asian	0.0121%	8,281

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val1732Ile
Coding: c.5194G>A
MANE Select: NM_016252
dbSNP: rs61757640
Type: single nucleotide variant
Location: chr2:32464761 (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-val1732ile (accessed [today's date]).

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