Is BRD8 p.Ile673Val (c.2017A>G) pathogenic?

BRD8 p.Ile673Val (c.2017A>G) is classified Uncertain significance in BRD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely benign (0.0837); Rare (popmax 0.103%, afr).

How common is BRD8 p.Ile673Val (c.2017A>G) in the general population?

BRD8 p.Ile673Val (c.2017A>G) is rare (popmax 0.103%, afr) (gnomAD).

What do computational predictors say about BRD8 p.Ile673Val (c.2017A>G)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

BRD8 p.Ile673Val

c.2017A>G · rs141585213 · VCV2296018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.46	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 4.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 1,209 bp · p 0.00052 · regional, not allelic
Overall
CADD	19.64	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 0.103% African / African-American · 77/75,034 alleles

Filtering AF 0.0841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0773%

Overall 0.00508% 82/1,614,158 alleles · rare exomes 34/1,461,888 · genomes 48/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.103%	974
Remaining individualsnot grpmax-eligible	0.0064%	15,628
Admixed American	0.00167%	60,006

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: BRD8
Protein: p.Ile673Val
Coding: c.2017A>G
MANE Select: NM_139199
dbSNP: rs141585213
Type: single nucleotide variant
Location: chr5:138163200 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.92

Full BRD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRD8 p.Ala165Val Uncertain significance ★ ⚠ same type
BRD8 p.Ala211Thr Uncertain significance ★ ⚠ same type
BRD8 p.Ala264Val Uncertain significance ★ ⚠ same type
BRD8 p.Ala273Ser Uncertain significance ★ ⚠ same type
BRD8 p.Ala314Val Uncertain significance ★ ⚠ same type
BRD8 p.Ala331Thr Uncertain significance ★ ⚠ same type
BRD8 p.Ala437Thr Uncertain significance ★ ⚠ same type
BRD8 p.Ala553Val Uncertain significance ★ ⚠ 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/brd8-p-ile673val (accessed [today's date]).

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