Is BRPF1 p.Pro70Ser (c.208C>T) pathogenic?

BRPF1 p.Pro70Ser (c.208C>T) is classified Likely benign in BRPF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-23). AlphaMissense: likely benign (0.0625); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with BRPF1 p.Pro70Ser (c.208C>T)?

BRPF1 p.Pro70Ser (c.208C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BRPF1 p.Pro70Ser (c.208C>T) in the general population?

BRPF1 p.Pro70Ser (c.208C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about BRPF1 p.Pro70Ser (c.208C>T)?

AlphaMissense predicts likely benign (score 0.0625) — an in-silico prediction, not a clinical call.

BRPF1 p.Pro70Ser

c.208C>T · VCV3261855

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0625 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0625	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -4.47	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 4.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 5,121 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	22.1	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 0.0156% East Asian · 7/44,876 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00105% 17/1,613,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,411
South Asian	0.00988%	10,121
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: BRPF1
Protein: p.Pro70Ser
Coding: c.208C>T
MANE Select: NM_001003694
Type: single nucleotide variant
Location: chr3:9734348 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 66 PDB
Residue 70: a UniProt-annotated variant site (in idddfp); the 'disordered' region; the 'interaction with kat6a and kat6b' region

Full BRPF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRPF1 p.Pro70Ala Uncertain significance ★ ⚠ same residue
BRPF1 p.Pro70Leu Uncertain significance ★ ⚠ same residue
BRPF1 p.Arg182Trp Uncertain significance ★★ same condition
BRPF1 p.Arg319His Uncertain significance ★★ ⚠ same condition
BRPF1 p.Asp445Asn Uncertain significance ★★ ⚠ same condition
BRPF1 p.Cys858Phe Uncertain significance ★★ ⚠ same condition
BRPF1 p.Glu1211Lys Uncertain significance ★★ ⚠ same condition
BRPF1 p.Leu777Val 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/brpf1-p-pro70ser (accessed [today's date]).

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