Is BAK1 p.Arg207Thr (c.620G>C) pathogenic?

BAK1 p.Arg207Thr (c.620G>C) is classified Uncertain significance in BAK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: ambiguous (0.4789); Very rare (popmax 0.00267%, afr).

How common is BAK1 p.Arg207Thr (c.620G>C) in the general population?

BAK1 p.Arg207Thr (c.620G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about BAK1 p.Arg207Thr (c.620G>C)?

AlphaMissense predicts ambiguous (score 0.4789) — an in-silico prediction, not a clinical call.

BAK1 p.Arg207Thr

c.620G>C · rs1169211908 · VCV2546889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4789	ambiguous
REVEL	0.166	moderately benign-leaning
SaProt	LLR -7.87	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.41	donor gain · deltas
Constraint at this position
Conservation	phyloP 3.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,798 bp · p 3.2e-07 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 0.00267% African / African-American · 2/74,944 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,472
European (non-Finnish)	0.000509%	196,652

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: BAK1
Protein: p.Arg207Thr
Coding: c.620G>C
MANE Select: NM_001188
dbSNP: rs1169211908
Type: single nucleotide variant
Location: chr6:33573819 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.82 · 55 PDB
Residue 207: an α-helix

Full BAK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAK1 p.Arg127Pro Uncertain significance ★ ⚠ same type
BAK1 p.Arg169Trp Uncertain significance ★ ⚠ same type
BAK1 p.Arg206Gln Uncertain significance ★ ⚠ same type
BAK1 p.Arg36His Uncertain significance ★ ⚠ same type
BAK1 p.Arg76Trp Uncertain significance ★ ⚠ same type
BAK1 p.Asn124Ile Uncertain significance ★ ⚠ same type
BAK1 p.Asn124Ser Uncertain significance ★ ⚠ same type
BAK1 p.Asp160Asn 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/bak1-p-arg207thr (accessed [today's date]).

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