Is BRD8 p.Ser579Phe (c.1736C>T) pathogenic?

BRD8 p.Ser579Phe (c.1736C>T) is classified Uncertain significance in BRD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-28). AlphaMissense: likely benign (0.1492); Very rare (popmax 0.00329%, sas).

How common is BRD8 p.Ser579Phe (c.1736C>T) in the general population?

BRD8 p.Ser579Phe (c.1736C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about BRD8 p.Ser579Phe (c.1736C>T)?

AlphaMissense predicts likely benign (score 0.1492) — an in-silico prediction, not a clinical call.

BRD8 p.Ser579Phe

c.1736C>T · rs761070738 · VCV2398810

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1492 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1492	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -7.77	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 647 bp · p 1 · regional, not allelic
Overall
CADD	26.4	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 0.00329% South Asian · 3/91,070 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000806% 13/1,613,722 alleles · very rare exomes 11/1,461,566 · genomes 2/152,156 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,357
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000763%	131,086

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.Ser579Phe
Coding: c.1736C>T
MANE Select: NM_139199
dbSNP: rs761070738
Type: single nucleotide variant
Location: chr5:138164409 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.92
Residue 579: a modified residue (phosphoserine); the 'disordered' region

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-ser579phe (accessed [today's date]).

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