Is BRF2 p.Ala262Val (c.785C>T) pathogenic?

BRF2 p.Ala262Val (c.785C>T) is classified Uncertain significance in BRF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). AlphaMissense: likely benign (0.313); Ultra-rare (popmax 0.012%, afr).

How common is BRF2 p.Ala262Val (c.785C>T) in the general population?

BRF2 p.Ala262Val (c.785C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about BRF2 p.Ala262Val (c.785C>T)?

AlphaMissense predicts likely benign (score 0.313) — an in-silico prediction, not a clinical call.

BRF2 p.Ala262Val

c.785C>T · rs374484866 · VCV3135039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.313 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.313	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Overall
CADD	23.9	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 0.012% African / African-American · 9/74,940 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00626% 101/1,613,932 alleles · ultra-rare exomes 86/1,461,720 · genomes 15/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,327
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00695%	14,391
East Asian	0.00668%	14,963
South Asian	0.0022%	45,541

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.Ala262Val
Coding: c.785C>T
MANE Select: NM_018310
dbSNP: rs374484866
Type: single nucleotide variant
Location: chr8:37844965 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.79 · 22 PDB
Residue 262: 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.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
BRF2 p.Arg275Leu 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-ala262val (accessed [today's date]).

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