Is BRF1 p.Ser52Leu (c.155C>T) pathogenic?

BRF1 p.Ser52Leu (c.155C>T) is classified Uncertain significance in BRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-07). AlphaMissense: likely benign (0.1047); Very rare (popmax 0.005%, eas).

How common is BRF1 p.Ser52Leu (c.155C>T) in the general population?

BRF1 p.Ser52Leu (c.155C>T) is very rare (popmax 0.005%, eas) (gnomAD).

What do computational predictors say about BRF1 p.Ser52Leu (c.155C>T)?

AlphaMissense predicts likely benign (score 0.1047) — an in-silico prediction, not a clinical call.

BRF1 p.Ser52Leu

c.155C>T · rs1472627627 · VCV499049

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1047 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1047	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -9.09	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 11	GERP 1.1, phastCons 1
Overall
CADD	27.4	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 0.005% East Asian · 2/39,986 alleles

Filtering AF 0.000829% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00031%

Overall 0.000717% 11/1,534,240 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.005%	19,993
South Asian	0.00241%	41,463
Admixed American	0.00198%	50,620
European (non-Finnish)	0.000524%	190,718

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: BRF1
Protein: p.Ser52Leu
Coding: c.155C>T
MANE Select: NM_004926 · reported on NM_001519
dbSNP: rs1472627627
Type: single nucleotide variant
Location: chr14:105300475 (GRCh38)
Structure: AlphaFold pLDDT 59.70 · 2 PDB
Residue 52: the 'necessary and sufficient for the association with mrna decay enzymes and mrna decay activation' region

Full BRF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRF1 p.Pro292His Pathogenic/Likely pathogenic ★★ same type
BRF1 p.Ser226Leu Pathogenic/Likely pathogenic ★★ same type
BRF1 p.Ala565Ser Uncertain significance ★★ ⚠ same type
BRF1 p.Arg213Lys Uncertain significance ★★ ⚠ same type
BRF1 p.Arg216Gln Uncertain significance ★★ ⚠ same type
BRF1 p.Arg261Gln Uncertain significance ★★ ⚠ same type
BRF1 p.Arg302Trp Uncertain significance ★★ ⚠ same type
BRF1 p.Gly402Ser 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/brf1-p-ser52leu (accessed [today's date]).

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