Is BRF2 p.Met205Val (c.613A>G) pathogenic?

BRF2 p.Met205Val (c.613A>G) is classified Uncertain significance in BRF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0674); Very rare (popmax 0.000593%, nfe).

How common is BRF2 p.Met205Val (c.613A>G) in the general population?

BRF2 p.Met205Val (c.613A>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about BRF2 p.Met205Val (c.613A>G)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

BRF2 p.Met205Val

c.613A>G · VCV4216157

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -4.82	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 -1.3	GERP -4.2
Overall
CADD	0.002	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 0.000593% European (non-Finnish) · 7/1,179,928 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,712 alleles · very rare exomes 7/1,461,384 · genomes 0/152,328 · joint denominator

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: BRF2
Protein: p.Met205Val
Coding: c.613A>G
MANE Select: NM_018310
Type: single nucleotide variant
Location: chr8:37845137 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.79 · 22 PDB
Residue 205: an α-helix

Full BRF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRF2 p.Ala109Thr Uncertain significance ★ ⚠ same type
BRF2 p.Ala185Pro Uncertain significance ★ ⚠ same type
BRF2 p.Ala262Val Uncertain significance ★ ⚠ same type
BRF2 p.Ala93Thr Uncertain significance ★ ⚠ same type
BRF2 p.Arg102Trp Uncertain significance ★ ⚠ same type
BRF2 p.Arg127Gln Uncertain significance ★ ⚠ same type
BRF2 p.Arg203Gln Uncertain significance ★ ⚠ same type
BRF2 p.Arg265His 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/brf2-p-met205val (accessed [today's date]).

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