Is BRF1 p.Val604Ala (c.1811T>C) pathogenic?

BRF1 p.Val604Ala (c.1811T>C) is classified Likely benign in BRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: likely benign (0.0539); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BRF1 p.Val604Ala (c.1811T>C)?

BRF1 p.Val604Ala (c.1811T>C) is associated with Inborn genetic diseases (ClinVar).

How common is BRF1 p.Val604Ala (c.1811T>C) in the general population?

BRF1 p.Val604Ala (c.1811T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRF1 p.Val604Ala (c.1811T>C)?

AlphaMissense predicts likely benign (score 0.0539) — an in-silico prediction, not a clinical call.

BRF1 p.Val604Ala

c.1811T>C · VCV4599127

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0539 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0539	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -4.93	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 0.57	GERP -2.8, phastCons 0.002
Overall
CADD	0.373	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRF1
Protein: p.Val604Ala
Coding: c.1811T>C
MANE Select: NM_004926 · reported on NM_001519
Type: single nucleotide variant
Location: chr14:105212126 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB

Full BRF1 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

BRF1 p.Ala565Ser Uncertain significance ★★ ⚠ same condition
BRF1 p.Arg213Lys Uncertain significance ★★ ⚠ same condition
BRF1 p.Arg216Gln Uncertain significance ★★ ⚠ same condition
BRF1 p.Arg261Gln Uncertain significance ★★ ⚠ same condition
BRF1 p.Arg302Trp Uncertain significance ★★ ⚠ same condition
BRF1 p.Gly402Ser Uncertain significance ★★ ⚠ same condition
BRF1 p.Leu138Pro Uncertain significance ★★ ⚠ same condition
BRF1 p.Thr295Ala 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/brf1-p-val604ala (accessed [today's date]).

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