Is BRAF p.Gly28Ser (c.82G>A) pathogenic?

BRAF p.Gly28Ser (c.82G>A) is classified Uncertain significance in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-31). AlphaMissense: likely benign (0.0969); Very rare (popmax 0.00247%, eas).

How common is BRAF p.Gly28Ser (c.82G>A) in the general population?

BRAF p.Gly28Ser (c.82G>A) is very rare (popmax 0.00247%, eas) (gnomAD).

What do computational predictors say about BRAF p.Gly28Ser (c.82G>A)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

BRAF p.Gly28Ser

c.82G>A · rs1437317949 · VCV1677230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00247%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -8.44	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 3.9	GERP 2.6, phastCons 1
Overall
CADD	23.3	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 0.00247% East Asian · 1/40,476 alleles

Overall 0.000131% 2/1,524,898 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00247%	40,476
European (non-Finnish)	8.76e-05%	1,141,166

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: BRAF
Protein: p.Gly28Ser
Coding: c.82G>A
MANE Select: NM_004333
dbSNP: rs1437317949
Type: single nucleotide variant
Location: chr7:140924622 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 28: the 'disordered' region

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

Similar variants

BRAF p.Gly28Cys Uncertain significance ★ ⚠ same residue
BRAF p.Gly28= Likely benign ★ same residue
BRAF p.Gly28_Ala34del Uncertain significance ★ same residue
BRAF p.Ala246Pro Pathogenic ★★★ same type
BRAF p.Asn581Asp Pathogenic ★★★ same type
BRAF p.Asp594Val Pathogenic ★★★ same type
BRAF p.Cys532Tyr Likely pathogenic ★★★ same type
BRAF p.Gln257Arg Pathogenic ★★★ 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/braf-p-gly28ser (accessed [today's date]).

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