Is BAK1 p.Phe203Ser (c.608T>C) pathogenic?

BAK1 p.Phe203Ser (c.608T>C) is classified Uncertain significance in BAK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: likely pathogenic (0.6157); Very rare (popmax 8.47e-05%, nfe).

How common is BAK1 p.Phe203Ser (c.608T>C) in the general population?

BAK1 p.Phe203Ser (c.608T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BAK1 p.Phe203Ser (c.608T>C)?

AlphaMissense predicts likely pathogenic (score 0.6157) — an in-silico prediction, not a clinical call.

BAK1 p.Phe203Ser

c.608T>C · VCV3985794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6157 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6157	likely pathogenic
REVEL	0.177	moderately benign-leaning
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -0.35, phastCons 0.97
Regional constraint	o/e 0.69	unconstrained · MANE · 3,798 bp · p 3.2e-07 · regional, not allelic
Overall
CADD	19.82	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 8.47e-05% European (non-Finnish) · 1/1,179,984 alleles

Overall 6.84e-05% 1/1,461,838 alleles · very rare

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.Phe203Ser
Coding: c.608T>C
MANE Select: NM_001188
Type: single nucleotide variant
Location: chr6:33573831 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.82 · 55 PDB
Residue 203: 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.Arg207Thr 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

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-phe203ser (accessed [today's date]).

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